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Site-specific regulation of adult neurogenesis by dietary fatty acid content, vitamin E and flight exercise in European starlings
Abstract
Exercise is known to have a strong effect on neuroproliferation in mammals ranging from rodents to humans. Recent studies have also shown that fatty acids and other dietary supplements can cause an upregulation of neurogenesis. It is not known, however, how exercise and diet interact in their effects on adult neurogenesis. We examined neuronal recruitment in multiple telencephalic sites in adult male European starlings (Sturnus vulgaris) exposed to a factorial combination of flight exercise, dietary fatty acids and antioxidants. Experimental birds were flown in a wind tunnel following a training regime that mimicked the bird's natural flight behaviour. In addition to flight exercise, we manipulated the composition of dietary fatty acids and the level of enrichment with vitamin E, an antioxidant reported to enhance neuronal recruitment. We found that all three factors - flight exercise, fatty acid composition and vitamin E enrichment - regulate neuronal recruitment in a site-specific manner. We also found a robust interaction between flight training and vitamin E enrichment at multiple sites of neuronal recruitment. Specifically, flight training was found to enhance neuronal recruitment across the telencephalon, but only in birds fed a diet with a low level of vitamin E. Conversely, dietary enrichment with vitamin E upregulated neuronal recruitment, but only in birds not flown in the wind tunnel. These findings indicate conserved modulation of adult neurogenesis by exercise and diet across vertebrate taxa and indicate possible therapeutic interventions in disorders characterized by reduced adult neurogenesis.
... We captured starlings in southern Ontario, Canada, in July and maintained them in indoor aviaries until September, at which point they were randomly assigned to their treatment groups. This study is part of a group of studies on these birds (Hall et al., 2014;Nebel et al., 2012;Price et al., 2011), and complete methodology on husbandry, diets and training can be found in Hall et al. (2014). Briefly, starlings were fed one of four synthetic diets in a 2-factorial design that manipulated the fatty acid composition of the diet and the availability of a potent dietary antioxidant. ...
... We captured starlings in southern Ontario, Canada, in July and maintained them in indoor aviaries until September, at which point they were randomly assigned to their treatment groups. This study is part of a group of studies on these birds (Hall et al., 2014;Nebel et al., 2012;Price et al., 2011), and complete methodology on husbandry, diets and training can be found in Hall et al. (2014). Briefly, starlings were fed one of four synthetic diets in a 2-factorial design that manipulated the fatty acid composition of the diet and the availability of a potent dietary antioxidant. ...
Migratory birds undergo seasonal changes to muscle biochemistry. Nonetheless, it is unclear to what extent these changes are attributable to the exercise of flight itself versus endogenous changes. Using starlings (Sturnus vulgaris) flying in a wind tunnel, we tested the effects of exercise training, a single bout of flight and dietary lipid composition on pectoralis muscle oxidative enzymes and lipid transporters. Starlings were either unexercised or trained over 2 weeks to fly in a wind tunnel and sampled either immediately following a long flight at the end of this training or after 2 days recovery from this flight. Additionally, they were divided into dietary groups that differed in dietary fatty acid composition (high polyunsaturates versus high monounsaturates) and amount of dietary antioxidant. Trained starlings had elevated (19%) carnitine palmitoyl transferase and elevated (11%) hydroxyacyl-CoA dehydrogenase in pectoralis muscle compared with unexercised controls, but training alone had little effect on lipid transporters. Immediately following a long wind-tunnel flight, starling pectoralis had upregulated lipid transporter mRNA (heart-type fatty acid binding protein, H-FABP, 4.7-fold; fatty acid translocase, 1.9-fold; plasma membrane fatty acid binding protein, 1.6-fold), and upregulated H-FABP protein (68%). Dietary fatty acid composition and the amount of dietary antioxidants had no effect on muscle catabolic enzymes or lipid transporter expression. Our results demonstrate that birds undergo rapid upregulation of catabolic capacity that largely becomes available during flight itself, with minor effects due to training. These effects likely combine with endogenous seasonal changes to create the migratory phenotype observed in the wild.
... DHA is highly retained by vertebrates and it has been shown to be a dominant building block of brains in fishes , birds (Speake and Wood 2005), and mammals (Innis 2007). Laboratory feeding studies have shown that increased dietary intake of n-3 LC-PUFA facilitates brain growth and neuron proliferation in rodents (Kawakita et al. 2006), passerine birds (Hall et al. 2014), and freshwater (Lund et al. 2012) and marine fishes (Ishizaki et al. 2001). These dietaryinduced changes in brain development have also influenced cognitive skills of vertebrate consumers (Lund et al. 2014;Sugasini et al. 2017;Pilecky et al. 2021) and could thus potentially have a direct impact on their fitness in the wild (Boogert et al. 2018). ...
... Dietary intake and retention of energy in form of lipids has a substantial effect on the physiological development of consumers (Arts et al. 2009). However, our results indicate, in agreement with previous laboratory studies (Speake and Wood 2005;Lund et al. 2012;Hall et al. 2014), that the availability of structural lipids, especially DHA, and not just total lipids is key for brain development in these aquatic vertebrate consumers. Our findings suggest that the specialization of dietary niche in wild consumers on resources that have similar content of energy but differ in the content of n-3 LC-PUFA (Heissenberger et al. 2010;Twining et al. 2019;Scharnweber et al. 2021) can lead to intra-specific diversification of brain size. ...
Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are key structural lipids and their dietary intake is essential for brain development of virtually all vertebrates. The importance of n-3 LC-PUFA has been demonstrated in clinical and laboratory studies, but little is known about how differences in the availability of n-3 LC-PUFA in natural prey influence brain development of wild consumers. Consumers foraging at the interface of aquatic and terrestrial food webs can differ substantially in their intake of n-3 LC-PUFA, which may lead to differences in brain development, yet this hypothesis remains to be tested. Here we use the previously demonstrated shift towards higher reliance on n-3 LC-PUFA deprived terrestrial prey of native brown trout Salmo trutta living in sympatry with invasive brook trout Salvelinus fontinalis to explore this hypothesis. We found that the content of n-3 LC-PUFA in muscle tissues of brown trout decreased with increasing consumption of n-3 LC-PUFA deprived terrestrial prey. Brain volume was positively related to the content of the n-3 LC-PUFA, docosahexae-noic acid, in muscle tissues of brown trout. Our study thus suggests that increased reliance on diets low in n-3 LC-PUFA, such as terrestrial subsidies, can have a significant negative impact on brain development of wild trout. Our findings provide the first evidence of how brains of wild vertebrate consumers response to scarcity of n-3 LC-PUFA content in natural prey.
... DHA is highly retained by vertebrates and it has been shown to be a dominant building block of brains in fishes , birds (Speake and Wood 2005), and mammals (Innis 2007). Laboratory feeding studies have shown that increased dietary intake of n-3 LC-PUFA facilitates brain growth and neuron proliferation in rodents (Kawakita et al. 2006), passerine birds (Hall et al. 2014), and freshwater (Lund et al. 2012) and marine fishes (Ishizaki et al. 2001). These dietaryinduced changes in brain development have also influenced cognitive skills of vertebrate consumers (Lund et al. 2014;Sugasini et al. 2017;Pilecky et al. 2021) and could thus potentially have a direct impact on their fitness in the wild (Boogert et al. 2018). ...
... Dietary intake and retention of energy in form of lipids has a substantial effect on the physiological development of consumers (Arts et al. 2009). However, our results indicate, in agreement with previous laboratory studies (Speake and Wood 2005;Lund et al. 2012;Hall et al. 2014), that the availability of structural lipids, especially DHA, and not just total lipids is key for brain development in these aquatic vertebrate consumers. Our findings suggest that the specialization of dietary niche in wild consumers on resources that have similar content of energy but differ in the content of n-3 LC-PUFA (Heissenberger et al. 2010;Twining et al. 2019;Scharnweber et al. 2021) can lead to intra-specific diversification of brain size. ...
1. Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are key structural lipids and their dietary intake is essential for brain development of virtually all vertebrates. The importance of n-3 LC-PUFA has been demonstrated in clinical and laboratory studies, but little is known about how differences in availability of n-3 LC-PUFA in natural prey influence brain development of wild consumers. The availability of n-3 LC-PUFA in the prey communities is driven by primary producers and it is therefore distributed heterogeneously, but predictably across ecosystems, being higher in aquatic than in terrestrial food webs. Consequently, the numerous consumers foraging on the interface of aquatic and terrestrial food webs can differ substantially in their intake of n-3 LC-PUFA, which may lead to in brain development, yet, this hypothesis still remains to be tested.
2. Here we use the previously demonstrated shift towards higher reliance on n-3 LC-PUFA deprived terrestrial prey of native brown trout Salmo trutta living in sympatry with invasive brook trout Salvelinus fontinalis to explore this hypothesis.
3. We found that the content of n-3 LC-PUFA in muscle tissues of brown trout decreased with increasing consumption of n-3 LC-PUFA deprived terrestrial prey. Brain volume was positively related to content of the n-3 LC-PUFA, docosahexaenoic acid, in muscle tissues of brown trout.
4. Our study thus suggests that increased reliance on low quality diet of n-3 LC-PUFA deprived subsidies from terrestrial food web can have a significant negative impact on brain development of wild trout. These findings provide the first evidence of an intra-specific link between n-3 LC-PUFA content in natural prey and brain size of wild vertebrate consumers.
5. Ongoing global change is predicted to reduce the availability of dietary n-3 LC-PUFA across food webs. Therefore, our findings emphasise the need for further research on how wild consumers adapt to the shortage of dietary n-3 LC-PUFA in order to maintain optimal development and functioning of their brain, which is crucial for their fitness.
... This substage requires flexibility and coordination of morphology, behavior, and physiology given the quixotic environmental conditions birds may face in early spring. Observational studies note that migratory behavior changes as birds approach breeding areas and begin to search widely for optimal habitats (Hahn et al., 1995). Studies of captive birds, report changes in intensity of migratory restlessness and orientation near the conclusion of the migratory period, suggesting transition to more wandering and searching behaviors expressed even in captivity (Helms, 1963;Wiltschko et al., 1980;Ramenofsky et al., 2003). ...
... Such natural doping on n-3 f0035 FIGURE 47.6 A simplified schematic of a physiological regulatory network that indicates how certain dietary fatty acids serve as key "integrators" that interact with multiple systems (subnetworks) and each other, thereby ensuring an appropriate match between phenotype and environmental conditions. Dietary fatty acids have been shown to influence the immune system (Nebel et al., 2012), neurogenesis (Hall et al., 2013), and neuroendocrine control of metabolism (Casagrande et al., 2020), and oxidative status . The three hypotheses (membrane, fuel, and signal), and the evidence that supports or refutes them are described in the text. ...
Migratory birds face a host of physiological challenges during their annual peregrinations including (a) maintaining synchrony with the changing environments encountered as they migrate by relying on environmental cues in conjunction with endogenous rhythms to coordinate patterns of movement and stasis; (b) using fats as their primary fuel to satisfy the very high-metabolic costs of continual flapping flight—this requires more oxygen and lipid transporters and energy production, produces more reactive species, produces less metabolic water, and generates more heat. Overcoming these challenges requires flexible (reversble) modifications to physiology including key components of the endocrine, circulatory, respiratory, antioxidant, and thermoregulatory systems, all of which we have described here. A major theme of this chapter is that the life history of a typical migratory bird includes two migration stages—vernal and autumnal—that occur at separate times of the year under differing environmental conditions, that are regulated by unique neuroendocrine mechanisms, and that present somewhat similar yet distinct physiological challenges. Major gaps remain in our understanding of both the network of specific molecules and regulatory relationships that maintain and adjust homeostasis across the life history stages, and especially how the concentrations of key molecules and the relative strengths of certain regulatory relationships change with the context and the conditions of vernal and autumnal migration. More integrative studies (from molecules to genes to physiology to whole organisms) that are also comparative (multiple systems, multiple tissues within the same individual, migration state vs. nonmigration periods, vernal vs. autumnal migration, multiple species that differ in migration strategy) are needed in order to gain a more complete understanding of how the environment influences migration of birds, how birds overcome the multifaceted physiological challenges of migration, and how individuals will cope with the challenges of climate change.
... Convex hull surface (µm 2 ) Convex hull volume (µm 3 ) (Hall et al., 2014). During their stopover in the Bay of Fundy, semipalmated sandpipers and semipalmated plovers are exposed to a diet that is extremely high in PUFAs (Maillet and Weber, 2007;Nagahuedi et al., 2009;Weber, 2009). ...
... During their stopover in the Bay of Fundy, semipalmated sandpipers and semipalmated plovers are exposed to a diet that is extremely high in PUFAs (Maillet and Weber, 2007;Nagahuedi et al., 2009;Weber, 2009). As previously shown (Hall et al., 2014) and as TABLE 4 | Mean values, standard deviation, corresponding standard errors and significant differences between Type I and Type II radial astrocytes of hippocampal V area ( Figure 6). ...
Little is known about environmental influences on radial glia-like (RGL) α cells (radial astrocytes) and their relation to neurogenesis. Because radial glia is involved in adult neurogenesis and astrogenesis, we investigated this association in two migratory shorebird species that complete their autumnal migration using contrasting strategies. Before their flights to South America, the birds stop over at the Bay of Fundy in Canada. From there, the semipalmated sandpiper (Calidris pusilla) crosses the Atlantic Ocean in a non-stop 5-day flight, whereas the semipalmated plover (Charadrius semipalmatus) flies primarily overland with stopovers for rest and feeding. From the hierarchical cluster analysis of multimodal morphometric features, followed by the discriminant analysis, the radial astrocytes were classified into two main morphotypes, Type I and Type II. After migration, we detected differential changes in the morphology of these cells that were more intense in Type I than in Type II in both species. We also compared the number of doublecortin (DCX)-immunolabeled neurons with morphometric features of radial glial–like α cells in the hippocampal V region between C. pusilla and C. semipalmatus before and after autumn migration. Compared to migrating birds, the convex hull surface area of radial astrocytes increased significantly in wintering individuals in both C. semipalmatus and C. pusilla. Although to a different extent we found a strong correlation between the increase in the convex hull surface area and the increase in the total number of DCX immunostained neurons in both species. Despite phylogenetic differences, it is of interest to note that the increased morphological complexity of radial astrocytes in C. semipalmatus coincides with the fact that during the migratory process over the continent, the visuospatial environment changes more intensely than that associated with migration over Atlantic. The migratory flight of the semipalmated plover, with stopovers for feeding and rest, vs. the non-stop flight of the semipalmated sandpiper may differentially affect radial astrocyte morphology and neurogenesis.
... Based on neuronal morphology, these neurons can be classified into elongated (E; long bipolar cell body), multipolar (M) and spherical (S) neuron types. E neurons migrate to the integration point, while M and S neurons are recruited and integrated to an existing neural circuit ( Balthazart, Boseret, Konkle, Hurley, & Ball, 2008;Hall et al., 2013). Interestingly, hippocampal neurogenesis correlates with the learning and memory, as required by a species. ...
... Then, sections were incubated with DCX primary antibody (1:1000; Cat# sc-8066, Santa Cruz Biotechnology, Heidelberg, Germany) initially for 2 h at the room temperature and subsequently overnight at 4 °C. This antibody is specific and has been previously used for DCX IHC in other songbirds ( Hall et al., 2013;Surbhi et al., 2016). Following day, sections were PBS-washed and sequentially incubated for 2 h each with biotin conjugated secondary antibody (1:200; B2770; Invitrogen, Eugene, USA) and avidin biotin complex (1:55; Elite ABC Kit, Vector Laboratories, Burlingame, CA). ...
Periodic day-night environment shapes the temporal pattern in the behaviour and physiology (e.g. 24-h activity-rest and sleep-wake cycles) and the advanced brain function, such as learning, memory and decision making. In a previous study, we showed the abolition of 24-h rhythm in the activity-rest pattern, and an attenuated cognitive performance in diurnal Indian house crows (Corvus splendens) under constant light (no-night; LL) environment. Present study extended this, and investigated LL-induced effects on the neurogenesis (birth, maturation and neurite complexity of new born neurons) in the hippocampus and caudal nidopallium, the brain regions directly associated with learning and cognition in birds. We performed immunohistochemistry of doublecortin (DCX; a neurogenesis marker) and tyrosine hydroxylase (TH, a key enzyme of the dopamine biosynthesis) in the brain section containing hippocampus or caudal nidopallium of Indian house crows exposed for 2 weeks to LL, with controls maintained under 12L:12D. As expected, crows showed arrhythmicity with a significantly reduced rest period in the 24-h activity-rest pattern, and a decreased cognitive performance when tested for the spatial and pattern association learning tasks under LL. Importantly, there was a significant decrease in DCX-immunoreactive (ir) cells and, as shown by Sholl analysis, in the complexity of DCX-ir neurites in both, the hippocampus and caudal nidopallium of crows under LL, as compared to those under 12L:12D. The anatomical proximity of DCX-ir neurons with TH-ir fibers suggested a functional association of the new born hippocampal and caudal nidopallial neurons with the learning, and perhaps cognition in Indian house crows. These results give insights into possible impact of the loss of night on brain health and functions in an emerging ecosystem in which other diurnal species including humans may be inadvertently exposed to an illuminated night, such as in an overly lighted metropolitan urban habitat.
... Long distance flight also involves intense exercise, and exercise reliably increases hippocampal neurogenesis [78]. European starlings given flight exercise in a wind tunnel had greater levels of hippocampal neurogenesis than control birds without flight exercise [81]. Starlings flew in the wind tunnel for 15 consecutive days for durations that increased up to 180 min/ day, followed by a final day of voluntary flight of up to 4 h. ...
... The same study of starling wind tunnel flight also showed that a diet high in polyunsaturated fatty acids (PUFA) led to less hippocampal neurogenesis than a diet low in PUFAs [81]. Semipalmated sandpipers during their stopover in the Bay of Fundy consume a diet extremely high in PUFAs [2,82,83]. ...
Long distance migratory birds find their way by sensing and integrating information from a large number of cues in their environment. These cues are essential to navigate over thousands of kilometers and reach the same breeding, stopover, and wintering sites every year. The semipalmated sandpiper (Calidris pusilla) is a long-distance migrant that breeds in the arctic tundra of Canada and Alaska and winters on the northeast coast of South America. Its fall migration includes a 5,300-kilometer nonstop flight over the Atlantic Ocean. The avian hippocampus has been proposed to play a central role in the integration of multisensory spatial information for navigation. Hippocampal neurogenesis may contribute to hippocampal function and a variety of factors including cognitive activity, exercise, enrichment, diet and stress influence neurogenesis in the hippocampus. We quantified hippocampal neurogenesis and volume in adult migrating and wintering semipalmated sandpipers using stereological counts of doublecortin (DCX) immunolabeled immature neurons. We found that birds captured in the coastal region of Bragança, Brazil during the wintering period had more DCX positive neurons and larger volume in the hippocampus than individuals captured in the Bay of Fundy, Canada during fall migration. We also estimate the number of NeuN immunolabeled cells in migrating and wintering birds and found no significant differences between them. These findings suggest that, at this time window, neurogenesis just replaced neurons that might be lost during the transatlantic flight. Our findings also show that in active fall migrating birds, a lower level of adult hippocampal neurogenesis is associated with a smaller hippocampal formation. High levels of adult hippocampal neurogenesis and a larger hippocampal formation found in wintering birds may be late occurring effects of long distance migratory flight or the result of conditions the birds experienced while wintering.
... It is also likely that most laboratory rodent and avian studies showing environmental effects on hippocampal neurogenesis (e.g., review in Barnea & Pravosudov, 2011) also detect neurogenesis rates much below the normal "base" levels, which could indeed be improved by even slight environmental changes in extremely impoverished lab conditions. For example, Hall et al. (2014) reported significant effects of flight exercise on adult neurogenesis using doublecortin staining to quantify neurogenesis in adult starlings (Sturnus vulgaris) captured and maintained in a laboratory. The number of new neurons reported in Hall et al. (2014) is much smaller than that reported for wild chickadees using the same method (LaDage et al., 2010;Roth et al., 2012). ...
... For example, Hall et al. (2014) reported significant effects of flight exercise on adult neurogenesis using doublecortin staining to quantify neurogenesis in adult starlings (Sturnus vulgaris) captured and maintained in a laboratory. The number of new neurons reported in Hall et al. (2014) is much smaller than that reported for wild chickadees using the same method (LaDage et al., 2010;Roth et al., 2012). Even though starlings are not a food-caching species and so likely have lower levels of hippocampal neurogenesis , it is also very likely that these numbers are much reduced due to captivity and so additional exercise might simply reduce captivity-related stress's effect on neurogenesis, rather than have an additive effect on the naturally present baseline. ...
... It is also likely that most laboratory rodent and avian studies showing environmental effects on hippocampal neurogenesis (e.g., review in Barnea & Pravosudov, 2011) also detect neurogenesis rates much below the normal "base" levels, which could indeed be improved by even slight environmental changes in extremely impoverished lab conditions. For example, Hall et al. (2014) reported significant effects of flight exercise on adult neurogenesis using doublecortin staining to quantify neurogenesis in adult starlings (Sturnus vulgaris) captured and maintained in a laboratory. The number of new neurons reported in Hall et al. (2014) is much smaller than that reported for wild chickadees using the same method (LaDage et al., 2010;Roth et al., 2012). ...
... For example, Hall et al. (2014) reported significant effects of flight exercise on adult neurogenesis using doublecortin staining to quantify neurogenesis in adult starlings (Sturnus vulgaris) captured and maintained in a laboratory. The number of new neurons reported in Hall et al. (2014) is much smaller than that reported for wild chickadees using the same method (LaDage et al., 2010;Roth et al., 2012). Even though starlings are not a food-caching species and so likely have lower levels of hippocampal neurogenesis , it is also very likely that these numbers are much reduced due to captivity and so additional exercise might simply reduce captivity-related stress's effect on neurogenesis, rather than have an additive effect on the naturally present baseline. ...
... Thus, they are an ideal natural system to study how the endogenous antioxidant system responds to flight training, dietary antioxidants, and dietary fat. We used European starlings Sturnus vulgaris as representative songbirds for this study because they are abundant in the New World and Old World, are omnivorous, acclimate well to captivity and new diets, and have been successfully trained and flown in wind tunnels in other studies (Nebel et al. 2012, Hall et al. 2014, Casagrande et al. 2020. Hatch year European starlings were caught at a dairy farm 20 km north of the Advanced Facility for Avian Research (AFAR), University of Western Ontario, London, Ontario, prior to fall migration in 2015 (19-23 August). ...
Ecologically relevant factors such as exercise and diet quality can directly influence how multifaceted physiological systems work; however, little is known about how such factors directly and interactively affect key components of the antioxidant system in multiple tissues of migratory songbirds. We tested 3 main hypotheses across three tissues in European starlings fed diets with more or less antioxidants (anthocyanins) and long‐chain omega‐6 polyunsaturated fats (18:2n6) while being flight‐trained in a wind tunnel. Stimulatory effect of flight: flight‐training stimulated the antioxidant system in that 1) plasma oxidative damage (dROMs) was reduced during a given acute flight, and contrary to our predictions, 2) antioxidant capacity (OXY or ORAC) and oxidative damage in plasma (dROMs), flight‐muscle, and liver (LPO) of flight‐trained birds were similar to that of untrained birds (i.e. not flown in a wind tunnel). Flight‐trained birds that expended more energy per unit time (kJ min⁻¹) during their longest, final flight decreased antioxidant capacity (OXY) the most during the final flight. Dietary fat quality effect: contrary to our predictions, dietary 18:2n‐6 did not influence oxidative status even after flight training. Dietary antioxidant effect: flight‐trained birds supplemented with dietary anthocyanins did not have higher antioxidant capacity in plasma (OXY), or liver and flight‐muscle (ORAC) compared to untrained birds. Counterintuitively, oxidative damage (dROMs) was higher in flight‐trained supplemented birds compared to unsupplemented birds after an acute flight. In sum, the antioxidant system of songbirds flexibly responded to changes in availability of dietary antioxidants as well as increased flight time and effort, and such condition‐dependent, individual‐level, tissue‐specific responses to the oxidative costs of long‐duration flights apparently requires recovery periods for maintaining oxidative balance during migration.
... Omega-3 LC-PUFAs, particularly DHA, are indispensable for optimal functioning of neural tissues in all vertebrates and in some invertebrates [27] (Box 1). Deprivation of n-3 LC-PUFA has negative effects on brain growth and neuron proliferation in laboratory studies on freshwater fishes [74], marine fishes [75], amphibians [76], passerine birds [77], and rodents [78]. The number of neurons and their connections in the whole brain is the best available determinant of the brain information processing capacity [79], yet the effect of DHA on neuron numbers in the whole brain has not been studied. ...
The physiological dependence of animals on dietary intake of vitamins, amino
acids, and fatty acids is ubiquitous. Sharp differences in the availability of
these vital dietary biomolecules among different resources mean that consumers
must adopt a range of strategies to meet their physiological needs.We review the
emerging work on omega-3 long-chain polyunsaturated fatty acids, focusing
predominantly on predator–prey interactions, to illustrate that trade-off between
capacities to consume resources rich in vital biomolecules and internal synthesis
capacity drives differences in phenotype and fitness of consumers. This can then
feedback to impact ecosystem functioning. We outline how focus on vital dietary
biomolecules in eco-eco-devo dynamics can improve our understanding of
anthropogenic changes across multiple levels of biological organization.
... There has been some controversial research that has yet to be resolved regarding the ability of LCPU-FAs to boost flight enzymes. In one study on bobwhite quail Colinus virginianus, which are not longdistance migrants, those fed high doses of EPA and DHA increased the amount of oxidative enzymes in their flight muscles by 58−90%, a level only seen in migrating shorebirds (Nagahuedi et al. 2009), some mammals, red-eyed vireos Vireo olivaceus (Pierce et al. 2005), and European starlings Sturnus vulgaris (Hall et al. 2014). In vitro, bird muscle EPA and DHA increase the mitochondrial respiratory chain efficiency and also the basal and maximal oxygen con-sumption in muscles (Young 2019) which allow more complete utilization of fuel and a more efficient oxidation. ...
This review highlights diatoms and their production of fatty acids at Arctic ice edges
and temperate estuaries as strategic in initiating high spring productivity. As important as their energy production is their synthesis de novo of omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), which are bioactive molecules fundamental to maintaining ecosystem processes, and are necessary for reproduction and growth for the entire marine food web. Without these fatty acids, consumers can suffer poor reproduction and growth even with sufficient energy intake, and shorebirds may need LCPUFAs for nonstop long-hop migration. Timing of high energy fatty acid and LCPUFA production by diatoms coincides with growth and reproduction of consumer populations, with the arrival of seabirds in the Arctic and staging of shorebirds in estuaries. The switch from diatom production of carbohydrates to fatty acids is triggered by changes in chemical and physical environmental factors, which can be muted by factors such as climate change or habitat modification. Higher ocean temperatures and lower pH from climate change alters the ability of diatoms to make LCPUFAs, and habitat degradation reduces the numbers of diatoms in the area, subsequently reducing the amounts of LCPUFA produced. Changes in LCPUFA output could impact functionality of ice-edge and estuarine ecosystems, impacting shorebird migration and consumer productivity. Research is scarce on marine consumer reproduction and growth comparing quantity vs. quality of ingested saturated, monounsaturated, and omega-3 LCPUFAs, and nonexistent for seabirds and shorebirds. Future studies of marine food webs should include the role of diatoms and their contribution of not just energy, but also LCPUFAs to the food web.
... DHA is highly retained by vertebrates (Pilecky et al. 2021) and it has been shown to be a dominant building block of brain of shes ), birds (Speake & Wood 2005), and mammals (Innis 2007). Laboratory feeding studies have shown that increased dietary intake of n-3 LC-PUFA facilitates brain growth and neuron proliferation in rodents (Kawakita et al. 2006), passerine birds (Hall et al. 2014), and freshwater (Lund et al. 2012) and marine shes (Ishizaki et al. 2001). These dietary induced changes in brain development have also been shown to in uence cognitive skills of vertebrate consumers (Lund et (Twining et al. 2016;Marzetz et al. 2017). ...
Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) are key structural lipids and their dietary intake is essential for brain development of virtually all vertebrates. The importance of n-3 LC-PUFA has been demonstrated in clinical and laboratory studies, but little is known about how differences in availability of n-3 LC-PUFA in natural prey influence brain development of wild consumers. The numerous consumers foraging on the interface of aquatic and terrestrial food webs can differ substantially in their intake of n-3 LC-PUFA, which may lead to differences in brain development, yet, this hypothesis remains to be tested. Here we use the previously demonstrated shift towards higher reliance on n-3 LC-PUFA deprived terrestrial prey of native brown trout Salmo trutta living in sympatry with invasive brook trout Salvelinus fontinalis to explore this hypothesis. We found that the content of n-3 LC-PUFA in muscle tissues of brown trout decreased with increasing consumption of n-3 LC-PUFA deprived terrestrial prey. Brain volume was positively related to content of the n-3 LC-PUFA, docosahexaenoic acid, in muscle tissues of brown trout. Our study thus suggests that increased reliance on low quality diet of n-3 LC-PUFA deprived subsidies can have a significant negative impact on brain development of wild trout. Our findings are important, because ongoing global change is predicted to reduce the availability of dietary n-3 LC-PUFA across food webs and we showed here a first evidence of how brain of wild vertebrate consumers response to scarcity of n-3 LC-PUFA content in natural prey.
... wind tunnels in other studies (Hall et al. 2014;Casagrande et al. 2020 (Dolbeer 1982;Cabe 1993). Therefore, flights ranging from 1-3 hours may constitute as intense exercise for the starlings in our experiment. ...
Ecologically-relevant factors such as exercise and diet quality can directly influence how physiological systems work including those involved in maintaining oxidative balance; however, to our knowledge, no studies to date have focused on how such factors directly affect expression of key components of the endogenous antioxidant system (i.e., transcription factors, select antioxidant genes, and corresponding antioxidant enzymes) in several metabolically active tissues of a migratory songbird. We conducted a 3-factor experiment that tested the following hypotheses: (H1) Daily flying over several weeks increases the expression of transcription factors NRF2 and PPARs as well as endogenous antioxidant genes (i.e., CAT, SOD1, SOD2, GPX1, GPX4), and upregulates endogenous antioxidant enzyme activities (i.e., CAT, SOD, GPx). (H2) Songbirds fed diets composed of more 18:2n-6 PUFA are more susceptible to oxidative damage and thus upregulate their endogenous antioxidant system compared to when fed diets with less PUFA. (H3) Songbirds fed dietary anthocyanins gain additional antioxidant protection and thus upregulate their endogenous antioxidant system less compared to songbirds not fed anthocyanins. Flight training increased the expression of 3 of the 6 antioxidant genes and transcription factors measured in the liver, consistent with H1, but for only one gene (SOD2) in the pectoralis. Dietary fat quality had no effect on antioxidant pathways (H2) whereas dietary anthocyanins increased the expression of select antioxidant enzymes in the pectoralis, but not in the liver (H3). These tissue-specific differences in response to flying and dietary antioxidants are likely explained by functional differences between tissues as well as fundamental differences in their turnover rates. The consumption of dietary antioxidants along with regular flying enables birds during migration to stimulate the expression of genes involved in antioxidant protection likely through increasing the transcriptional activity of NRF2 and PPARs, and thereby demonstrates for the first time that these relevant ecological factors affect the regulation of key antioxidant pathways in wild birds. What remains to be demonstrated is how the extent of these ecological factors (i.e., intensity or duration of flight, amounts of dietary antioxidants) influences the regulation of these antioxidant pathways and thus oxidative balance.
... After 48 days of daily exercise-training, we randomly selected 8 male zebra finches from the unexercised group and 4 male zebra finches from the exercised group to be gavaged with 150 μL (or 0.200 μmoles) of deuterated α-tocopherol (d 6 -RRRα-tocopherol acetate, a gift from Dr. John Lodge, St. Thomas' Hospital, London, hereafter: d 6 α-tocopherol or δD α-tocopherol to indicate the isotopic ratio) dissolved in olive oil. The gavaged amount of d 6 α-tocopherol (30 IU/dose) was chosen based on recommended supplements for poultry and to avoid any negative effects of over supplementation [62,63]. After 70 days of exercise-training, we randomly selected a second group of 4 male zebra finches from the exercised group to be gavaged with 150 μL of d 6 αtocopherol, and 3 male zebra finches from the unexercised group to be gavaged with 150 μL of olive oil. ...
Whether dietary antioxidants are effective for alleviating oxidative costs associated with energy-demanding life events first requires they are successfully absorbed in the digestive tract and transported to sites associated with reactive species production (e.g. the mitochondria). Flying birds are under high energy and oxidative demands, and although birds commonly ingest dietary antioxidants in the wild, the bioavailability of these consumed antioxidants is poorly understood. We show for the first time that an ingested lipophilic antioxidant, α-tocopherol, reached the mitochondria in the flight muscles of a songbird but only if they regularly exercise (60 min of perch-to-perch flights two times in a day or 8.5 km day⁻¹). Deuterated α-tocopherol was found in the blood of exercise-trained zebra finches within 6.5 hrs and in isolated mitochondria from pectoral muscle within 22.5 hrs, but never reached the mitochondria in caged sedentary control birds. This rapid pace (within a day) and extent of metabolic routing of a dietary antioxidant to muscle mitochondria means that daily consumption of such dietary sources can help to pay the inevitable oxidative costs of flight muscle metabolism, but only when combined with regular exercise.
... Such a relationship might have been predicted based on rodent studies, wherein time spent voluntarily running in a wheel correlates positively with AHN 64,85 . However, flight exercise was previously found not to be associated with DCX-expression in starlings 86 . Infrared tracking in the present study also recorded only vertical activity within the aviary, meaning individual differences in activity within a single horizontal zone or tier were not accounted for. ...
In commercial flocks of laying hens, keel bone fractures (KBFs) are prevalent and associated with behavioural indicators of pain. However, whether their impact is severe enough to induce a depressive-like state of chronic stress is unknown. As chronic stress downregulates adult hippocampal neurogenesis (AHN) in mammals and birds, we employ this measure as a neural biomarker of subjective welfare state. Radiographs obtained longitudinally from Lohmann Brown laying hens housed in a commercial multi-tier aviary were used to score the severity of naturally-occurring KBFs between the ages of 21–62 weeks. Individual birds’ transitions between aviary zones were also recorded. Focal hens with severe KBFs at 3–4 weeks prior to sampling (n = 15) had lower densities of immature doublecortin-positive (DCX+) multipolar and bipolar neurons in the hippocampal formation than focal hens with minimal fractures (n = 9). KBF severity scores at this time also negatively predicted DCX+ cell numbers on an individual level, while hens that acquired fractures earlier in their lives had fewer DCX+ neurons in the caudal hippocampal formation. Activity levels 3–4 weeks prior to sampling were not associated with AHN. KBFs thus lead to a negative affective state lasting at least 3–4 weeks, and management steps to reduce their occurrence are likely to have significant welfare benefits.
... In adult birds, new neurons are born in the lining of the lateral ventricles and migrate radially to different parts of the brain parenchyma guided by radial cell processes where they integrate into existing neuronal circuits (Alvarez-Buylla and Nottebohm, 1988). To date, adult neurogenesis has been found in birds belonging to widely unrelated avian orders including canaries (Alvarez-Buylla and Kirn, 1997;Boseret et al., 2007;Nottebohm, 2011;Vellema et al., 2014;Balthazart and Ball, 2016), zebra finches (Kim et al., 2006;Barkan et al., 2007;Cattan et al., 2015), song sparrows (LaDage et al., 2011;Wada et al., 2014), black capped chickadees (Barnea and Nottebohm, 1994;Hoshooley and Sherry, 2004;Aitken, 2015;Guitar, 2016), reed warblers (Barkan et al., 2016), cowbirds (Guigueno et al., 2016), starlings (Absil et al., 2003;Hall et al., 2014), ring doves (Ling and Cheng, 1995;Ling et al., 1997;Zuo, T 1998;Chen et al., 2006;Chen and Chen, 2007), turtle doves (Barkan et al., 2016), pigeons (Melleu et al., 2013(Melleu et al., , 2016Meskenaite et al., 2016;Mazengenya et al., 2017), parrots (Mazengenya et al., 2018), chicken (Capes-Davis et al., 2005;Nikolakopoulou et al., 2006a;Mezey et al., 2012) and quails (Nikolakopoulou et al., 2006b;Balthazart et al., 2010;Bardet et al., 2012;Mouriec and Balthazart, 2013;Nkomozepi et al., 2018b). However, the majority of neurogenesis studies in Japanese quails focused on sex steroid sensitive areas of the brain like the preoptic area (Balthazart et al., 2010;Bardet et al., 2012;Mouriec and Balthazart, 2013) and lateral septal nucleus (SL) (Nikolakopoulou et al., 2006b) in relation to sexual behavior. ...
Most avian neurogenesis studies focused on the song control system and little attention has been given to non-song birds such as the Japanese quail. However, the only few neurogenesis studies in quails mainly focused on the sex steroid sensitive areas of the brain such as the medial preoptic and lateral septal nuclei. Despite the important role the quail telencephalon plays in filial imprinting and passive avoidance learning, neurogenesis in this structure has been completely overlooked. The aim of this study was therefore to quantitatively determine how DCX expression in the Japanese quail telencephalon changes with post hatching age (3–12 weeks) and life history stage. In this study, DCX was used as a proxy for neuronal incorporation. Bipolar and multipolar DCX immunoreactive cells were observed in the entire telencephalon except for the entopallium and arcopallium. In addition, DCX expression in all the eight telencephalic areas quantified was strongly negatively correlated with post-hatching age. Furthermore, numbers of bipolar and multipolar DCX immunoreactive cells were higher in the juvenile compared to subadult and adult quails. In conclusion, neuronal incorporation in the quail telencephalon is widespread but it declines with post hatching age. In addition, the most dramatic decline in neuronal incorporation in the telencephalic areas quantified takes place just after the birds have attained sexual maturity.
... In mammalian adult brains, neurogenesis is restricted to the subgranular zone of the hippocampus and the subventricular zone of the lateral ventricle (Kaslin et al. 2008, Olaleye andIhunwo 2014). However, in avian brains new neurons are generated along the walls of the lateral ventricle and migrate radially to be inte-grated into the different circuits of the telencephalon (Hall et al. 2014, Vellema et al. 2010. ...
Most avian neurogenesis studies have previously focused on the song control system and little attention has been given to non‑song
birds. The objective of this study was to assess changes in neurogenesis associated with post‑hatching age (3‑12 weeks) in the Japanese
quail brain using proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunohistochemistry. PCNA‑immunoreactive
(ir) cells were observed mainly in the olfactory bulb ventricular zone, telencephalic ventricular zones and cerebellum. Fewer PCNA‑ir
cells were also observed in the hypothalamus, thalamus and bed nucleus of the stria terminalis. In telencephalic ventricular zones,
PCNA‑ir cells were concentrated ventrally and dorsally adjacent to the mesopallium and medial striatum, respectively. DCX‑ir cells were
observed in the olfactory bulb, telencephalon and cerebellum. Furthermore, DCX‑ir cells were scattered throughout the pallium except
in the entopallium and arcopallium, septal nuclei and striatum. Fewer DCX‑ir cells were also observed in the hippocampus and bed
nucleus of stria terminalis. The density of PCNA‑ir cells and DCX‑ir cells in all brain areas declined with post‑hatching age. In conclusion,
cell proliferation appears to be restricted to the ventricular zones whereas neuronal recruitment is more widespread in the olfactory
bulb, telencephalon and cerebellum. Postnatal neuronal incorporation appears to be absent in the diencephalon and mesencephalon.
Key words: neurogenesis, proliferating cell nuclear antigen, doublecortin, post‑hatching, Japanese quail brain, neuronal recruitment
... In spite of the enormous advances made during the last few decades regarding our understanding of the aetiology of age-related neurodegenerative disorders, great progress has been observed concerning the area of brain plasticity [194][195][196][197]. In subjects who have been involved in a physical exercise-based intervention protocol for people suffering these devastating neurodegenerative diseases [198][199][200][201][202]. ...
The effects of physical exercise on cerebral function have been reported in various research studies, thereby leading to better understanding of the brain's cellular mechanisms related to adaptations concerning physical exercise and the different cell responses which become compromised regarding chronic mechanisms. Relearning patterns of movement may thus be an alternative clinical approach affecting cognition and brain plasticity. Recent evidence has shown that neurogenesis can become increased by exercise; nevertheless, moderation mechanisms and the times involved in this process are not at all clear. This review thus provides an update for understanding physical exercise-induced neurogenesis, covering mediating mechanisms and maturation. This is important as glial cell mechanisms are signals activating the neurons and synaptically influencing them, as well as their development, transmission and plasticity via a series of secreted signals depending on contact in human beings. Neurogenesis thus represents a natural model for understanding how new neurons become regenerated and incorporated into brain circuits, thus representing therapeutic potential regarding delay or repair of brain damage caused by injury or disease.
... European Starling bird exercise trained in a wind tunnel that mimics the birds' natural flight were reported to display enhanced neuronal recruitment in the telencephalon, which houses the birds' cerebral cortex, amygdala, and hippocampus, during flight compared with another group of birds that were not trained. The enhanced neuronal recruitment in the trained group was paralleled by an increase in neurogenesis in the telencephalon, as revealed by doublecortin immunohistochemistry (Hall et al. 2014). These data suggest that the increase in adult neurogenesis and associated memory benefits may be a conserved effect of exercise in vertebrates. ...
Physical activity can enhance cognitive function and increase resistance against deleterious effects of stress on mental health. Enhanced cognitive function and stress resistance produced by exercise are conserved among vertebrates, suggesting that ubiquitous mechanisms may underlie beneficial effects of exercise. In the current review, we summarize the beneficial effects of exercise on cognitive function and stress resistance and discuss central and peripheral signaling factors that may be critical for conferring the effects of physical activity to brain circuits involved in cognitive function and stress. Additionally, it is suggested that norepinephrine and serotonin, highly conserved monoamines that are sensitive to exercise and able to modulate behavior in multiple species, could represent a convergence between peripheral and central exercise signals that mediate the beneficial effects of exercise. Finally, we offer the novel hypothesis that thermoregulation during exercise could contribute to the emotional effects of exercise by activating a subset of temperature-sensitive serotonergic neurons in the dorsal raphe nucleus that convey anxiolytic and stress-protective signals to forebrain regions. Throughout the review, we discuss limitations to current approaches and offer strategies for future research in exercise neuroscience.
... Here, vitamin supplementation may enhance or preserve cognitive performance, particularly learning and memory, by stimulating calcium related signaling, G protein functions, synaptic transmission, or even clearance of amyloid plaques (Adlard et al., 2005;Ding et al., 2006;Farmer et al., 2004;Soni et al., 2012;Vaynman et al., 2003;Yu et al., 2011). Additionally, vitamins have also been linked to the stimulation of adult hippocampal neurogenesis, although whether vitamins directly influence oligodendrogenesis remains unknown (Hall et al., 2014;Stangl and Thuret, 2009). However vitamins, including vitamin D and vitamin B12, are known to influence developmental myelination (Black, 2008;Chabas et al., 2013). ...
... Although neurogenesis is a well-preserved phenomenon in vertebrates [Grandel and Brand, 2013], in birds it appears more extensive compared to mammals: proliferation is restricted to the ventricular zone (VZ), but migration of progenitor cells and their integration into existing circuits occurs in several brain regions [reviewed by Barnea and Pravosudov, 2011]. Extensive studies have shown that the various stages of adult avian neurogenesis are regulated by a wide range of factors, such as hormones and seasonality [reviewed by Brenowitz, 2008]; diet and exercise [Hall et al., 2014]; age [reviewed by Barnea and Pravosudov, 2011]; climate and memory [Roth et al., 2012], and singing [Li et al., 2000]. Accordingly, the general assumption is that neurogenesis and neuronal recruitment provide a plastic substance for forming and storing memories. ...
GSK-3 (glycogen synthase kinase-3) is a serine/threonine kinase which is a critical regulator in neuronal signaling, cognition, and behavior. We have previously shown that unlike other vertebrates that harbor both α and β GSK-3 genes, the α gene is missing in birds. Therefore, birds can be used as a new animal model to study the roles of GSK-3β in behavior and in regulating adult neurogenesis. In the present study, we inhibited GSK-3β in brains of adult male zebra finches (Taeniopygia guttata) and accordingly investigated how this inhibition affects behavior and cell proliferation. Our results show that GSK-3 inhibition: (1) affects specific aspects of singing behavior, which might be related to social interactions in birds, and (2) differentially affects cell proliferation in various parts of the ventricular zone. Taken together, our study demonstrates a role of GSK-3β in regulating singing behavior and neuronal proliferation in birds and highlights the importance of GSK-3β in modulating cognitive abilities as well as social behavior. © 2015 S. Karger AG, Basel.
... The nutritional makeup of food in these experiments is important because it can have a substantial impact on brain circuits. For instance, differences in dietary fat intake affects the expression of doublecortin (DCX) in the brains of adult starlings (Hall et al., 2014), which suggests that composition of diet may have an effect on plasticity of neural circuits. A caveat is that even though DCX was formerly used as a immunohistological marker for neurogenesis, recent results call into the question the reliability of DCX as a marker of new neurons in the songbird brain (Vellema et al., 2014a, b). ...
Adverse environmental conditions can impact the life history trajectory of animals. Adaptive responses enable individuals to cope with unfavorable conditions, but altered metabolism and resource allocation can bear long-term costs. In songbirds, early developmental stress can cause lifelong changes in learned song, a culturally transmitted trait, and nestlings experiencing developmental stress develop a smaller song control nucleus HVCs. We investigated whether nutrition-related developmental stress impacts neurogenesis in HVC, which may explain how poor nutrition leads to smaller HVC volume. We provided different quality diets (LOW and HIGH) by varying the husks-to-seeds ratio to zebra finch families for the first 35 days after the young hatched (PHD). At PHD14-18 and again at nutritional independence (PHD35), juveniles were injected with different cell division markers. To monitor growth, we took body measures at PHD10, 17 and 35. At PHD35 the number of newly-recruited neurons in HVC and the rate of proliferation in the adjacent ventricular zone (VZ) were counted. Males raised on the LOW diet for their first weeks of life had significantly fewer new neurons in HVC than males raised on the HIGH diet. At the time when these new HVC neurons were born and labeled in the VZ (PHD17) the birds exposed to the LOW diet had significantly lower body mass. At PHD35 body mass or neuronal proliferation no longer differed. Our study shows that even transitory developmental stress can have negative consequences on the cellular processes underlying the development of neural circuits. This article is protected by copyright. All rights reserved.
© 2015 Wiley Periodicals, Inc.
... The number of DCX-ir cells may be an index of neurogenesis reflecting the number of young neurons alive in the brain of adult birds or adult neurons during the processes of dendrite-remodeling (e.g., Balthazart and Ball 2014). In consonance with the literature showing increased neurogenesis in the brain of adults housed in enriched environments (van Praag et al. 1999;Bruel-Jungerman et al. 2005;Meshi et al. 2006;Fan et al. 2014;Hall et al. 2014;Lindsey and Tropepe 2014), environmental enrichment also changed the index of neurogenesis in the brain of adult pigeons. Birds presented DCXir cells in several prosencephalic regions in addition to the hippocampus and ventricular neighborhoods (Boseret et al. 2007;Mezey et al. 2012;Melleu et al. 2013). ...
Neurogenesis in the adult brain appears to be phylogenetically conserved across the animal kingdom. In pigeons and other adult non-oscine birds, immature neurons are observed in several prosencephalic areas, suggesting that neurogenesis may participate in the control of different behaviors. The mechanisms controlling neurogenesis and its relevance to defensive behaviors in non-oscine birds remain elusive. Herein, the contribution of the environment to behavior and neurogenesis of pigeons was investigated. Adult pigeons (Columba livia, n = 6/group), housed in standard (SE) or enriched environment (EE) for 42 days, were exposed to an unfamiliar environment (UE) followed by presentation to a novel object (NO). Video recordings of UE+NO tests were analyzed and scored for latency, duration and frequency of angular head movements, peeping, grooming, immobility and locomotion. Twenty-four hours later, pigeons were submitted to the tonic immobility test (TI) and number of trials for TI and TI duration were scored, followed by euthanasia 2 h later. Brains were immunohistochemically processed to reveal doublecortin (DCX), a marker for newborn neurons. Compared to those housed in SE, the pigeons housed in EE responded to a NO with more immobility. In addition, the pigeons housed in EE presented longer TI, more DCX-immunoreactive (DCX-ir) cells in the hippocampus and fewer DCX-ir cells in the lateral striatum than those housed in SE. There was no correlation between the number of DCX-ir cells and the scores of immobility in behavioral tests. Together, these data suggest that enrichment favored behavioral inhibition and neurogenesis in the adult pigeons through different, parallel mechanisms.
... Fig. 4 A simplified schematic of a physiological regulatory network that indicates how certain dietary fatty acids serve as key ''integrators'' that interact with multiple systems (subnetworks) and each other, thereby ensuring an appropriate match between phenotype and environmental conditions (after Cohen et al. [2012]). Dietary fatty acids have been shown to influence the immune system (Nebel et al. 2012) and neurogenesis (Hall et al. 2013). The three hypotheses (membrane, fuel, and signal) whereby certain fatty acids affect exercise performance are described in the text. ...
... Exercise might also be involved in the captivity effects described above. Recent evidence from European starlings (Sturnus vulgaris) indicates that exercise increases neurogenesis in birds (Hall et al., 2014) as it does in mammals (van Praag, 2008). Starlings that flew in a wind tunnel for several hours per day for 15 days showed elevated hippocampal neurogenesis compared to control birds that did not fly. ...
... Fig. 4 A simplified schematic of a physiological regulatory network that indicates how certain dietary fatty acids serve as key ''integrators'' that interact with multiple systems (subnetworks) and each other, thereby ensuring an appropriate match between phenotype and environmental conditions (after Cohen et al. [2012]). Dietary fatty acids have been shown to influence the immune system (Nebel et al. 2012) and neurogenesis (Hall et al. 2013). The three hypotheses (membrane, fuel, and signal) whereby certain fatty acids affect exercise performance are described in the text. ...
Fatty-acid composition of fat stores affects exercise performance in a variety of vertebrates although few such studies focus on flying vertebrates such as migratory birds, which are exceptional exercisers. We first discuss the natural variation in quality of fat available in natural foods eaten by migratory birds and their behavioral preferences for specific fatty acids in these foods. We then outline three proposed hypotheses for how dietary fatty acids can affect exercise performance, and some of the evidence to date that pertains to these hypotheses with special emphasis on the exercise performance of migratory birds. In theory, selectively feeding on certain long-chain unsaturated fatty acids may be advantageous because (1) such fatty acids may be metabolized more quickly and may stimulate key facets of aerobic metabolism (fuel hypothesis); (2) such fatty acids may affect composition and key functions of lipid-rich cell membranes (membrane hypothesis); and (3) such fatty acids may directly act as signaling molecules (signal hypothesis). Testing these hypotheses requires cleverly designed experiments that can distinguish between them by demonstrating that certain fatty acids stimulate oxidative capacity, including gene expression and activity of key oxidative enzymes, and that this stimulation changes during exercise. © The Author 2014. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: [email protected]
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Songbird vocal behavior, physiology, and brains—including neurogenesis—change between seasons. We examined seasonal differences in neurogenesis in three brain regions associated with vocal production and learning, HVC (letter-based proper name), robust nucleus of the arcopallium (RA), and Area X, and two brain regions associated with auditory perception, caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM). To do this, we captured wild male and female European starlings (Sturnus vulgaris) in spring and fall, collected a blood sample, and minimized time from capture to tissue collection to limit suppressive effects of captivity on neurogenesis. We quantified neurogenesis using doublecortin (DCX) immunohistochemistry, counting new neurons of three DCX cell morphologies (multipolar, fusiform, and round). We found regional differences in types of morphologies expressed, and amount of neurogenesis across regions: NCM had more fusiform cells than all other regions, and RA had more round cells than other regions. Males had more neurogenesis in HVC in fall than in spring, but there was no seasonal difference in neurogenesis in HVC of females, perhaps reflecting sexually dimorphic vocal learning demands related to repertoire size and complexity. Plasma corticosterone was higher in spring than fall and was correlated with testis volume in males, but it was not correlated with another purported measure of stress, heterophil:lymphocyte ratio (HLR), nor with neurogenesis. Our results suggest that the addition of new neurons to specific regions and circuits may serve different functions for males and females, particularly in the context of vocal production, learning, and perceptual demands across seasons.
Neural plasticity in the hippocampus has been studied in a wide variety of model systems, including in avian species where the hippocampus underlies specialized spatial behaviours. Examples of such behaviours include navigating to a home roost over long distances by homing pigeons or returning to a potential nest site for egg deposit by brood parasites. The best studied example, however, is food storing in parids and the interaction between this behaviour and changes in hippocampus volume and neurogenesis. However, understanding the interaction between brain and behaviour necessitates research that includes studies with at least some form of captivity, which may itself affect hippocampal plasticity. Captivity might particularly affect spatial specialists where free-ranging movement on a large scale is especially important in daily, and seasonal, behaviours. This review examines how captivity might affect hippocampal plasticity in avian spatial specialists and specifically food-storing parids, and also considers how the effects of captivity may be mitigated by researchers studying hippocampal plasticity when the goal is understanding the relationship between behaviour and hippocampal change.
Lipids are abundant in the nervous system which is second only to adipose tissue. A major part of the lipids of the nervous system is found in myelin with about 70–80% of its dry mass. The major class of brain lipids is phospholipids and others include sphingolipids, gangliosides and cholesterol. These lipids are involved in the structure and function of cell membranes in the brain and display a variety of biological functions to maintain vital cellular processes at various levels; they are source of energy, serve as signalling molecules, and withstand structural integrity of cellular compartment and membranes. Lipids in the form of fatty acids participate actively in the development of the nervous system at embryonic and early postnatal stage and are crucial for its maintenance throughout adulthood. Dyslipidaemia is extensively considered as biomarker of diseases of the nervous system. It is therefore believed that these changes contribute in their own right by as yet incompletely understood mechanisms to those pathological processes. Human body is incapable to synthesize both LA and ALA endogenously, so their provision is exogenous with food and are classified as essential fatty acids. Correction of altered lipids level by exogenous supply is considered a most promising therapeutic approach.
A comprehensive description of overall brain architecture in molecular level is essential for understanding of behavioral and cognitive processes in health and diseases. Although fluorescent labeling of target proteins has been successfully established to visualize brain connectome, the molecular basis for diverse neurophysiological phenomena remains largely unknown. Here we report a brain-wide, molecular-level and microscale imaging of endogenous metabolites, in particular, lipids of mouse brain by using laser activated electron tunneling (LAET) and mass spectrometry. In this approach, atomic electron emission along with finely tuned laser beam size provides high resolution that can be down to sub-µm level to display spatial distribution of lipids in mouse brain slices. Electron-directed soft ionization has been achieved through exothermal capture of tunneling photoelectrons as well as unpaired electron initiated chemical bond cleavages. Regional Specific lipids including saturated, monounsaturated and polyunsaturated fatty acids as well as other lipids，which may be implicated in neurological signaling pathways, have been discovered by using this laser activated electron tunneling-based mass spectrometric imaging (LAET-MSI) technique.
Many songbirds are seasonally frugivorous and eat primarily fruit during migration and insects or seeds during nonmigratory periods. Previous work has suggested that most wild fruits may have inadequate protein for birds. Assessing the nutritional adequacy of fruit requires knowing the protein requirements of birds in relation to the composition of available fruits. We tested predictions of two hypotheses: (1) interspecific differences in protein requirements of birds are related to their foraging strategy; and (2) protein requirements of birds increase with demand, for example during migratory periods of the annual cycle. We measured the protein requirements of the omnivorous Hermit Thrush (Catharus guttatus) and the granivorous White-throated Sparrow (Zonotrichia albicollis) during nonmigratory and migratory stages of the annual cycle and compared the results with published estimates for other songbird species. In the nonmigratory state both species ate less, lost body mass, and had more negative nitrogen balance as dietary protein decreased. In the migratory state Hermit Thrushes lost body mass and had lower nitrogen balance but did not reduce food intake as dietary protein decreased, whereas White-throated Sparrows did not change body mass, food intake, or nitrogen balance as dietary protein decreased. Both species had lower protein requirements during migration (9.3 mg N day−1 and 15.8 mg N day−1, respectively) than during nonmigratory periods (53.1 mg N day−1 and 46.0 mg N day−1, respectively) when fed a diet containing 15.9 kJ g−1. These findings may partially explain how birds can adequately refuel on protein-limited foods such as fruits during migration.
Many songbirds are seasonally frugivorous and eat primarily fruit during migration and insects or seeds during
nonmigratory periods. Previous work has suggested that most wild fruits may have inadequate protein for birds. Assessing the
nutritional adequacy of fruit requires knowing the protein requirements of birds in relation to the composition of available fruits. We
tested predictions of two hypotheses: (1) interspecific differences in protein requirements of birds are related to their foraging strategy;
and (2) protein requirements of birds increase with demand, for example during migratory periods of the annual cycle. We measured the
protein requirements of the omnivorous Hermit Thrush (Catharus guttatus) and the granivorous White-throated Sparrow (Zonotrichia
albicollis) during nonmigratory and migratory stages of the annual cycle and compared the results with published estimates for other
songbird species. In the nonmigratory state both species ate less, lost body mass, and had more negative nitrogen balance as dietary
protein decreased. In the migratory state Hermit Thrushes lost body mass and had lower nitrogen balance but did not reduce food intake
as dietary protein decreased, whereas White-throated Sparrows did not change body mass, food intake, or nitrogen balance as dietary
protein decreased. Both species had lower protein requirements during migration (9.3 mg N day−1 and 15.8 mg N day−1, respectively)
than during nonmigratory periods (53.1 mg N day−1 and 46.0 mg N day−1, respectively) when fed a diet containing 15.9 kJ g−1. These
findings may partially explain how birds can adequately refuel on protein-limited foods such as fruits during migration.
The song-control system is a network of discrete nuclei in the songbird brain that controls the production and learning of birdsong and exhibits some of the best-studied neuroplasticity found in the adult brain. Photoperiodic growth of the song-control system during the breeding season is driven, at least in part, by the gonadal steroid testosterone. When acting on neural tissue, however, testosterone can be metabolized into 5α-dihydrotestosterone (DHT) or 17β-estradiol (E2), which activate different hormonal signaling pathways. By treating adult starlings with both testosterone metabolites and metabolite antagonists, we attempted to isolate the effects of androgen and estrogen treatment on neuroplasticity during photostimulation in male and female European starlings (Sturnus vulgaris). Photostimulation resulted in a large HVC volume typical of the breeding season in all treatments independent of hormone treatment. E2 had additional effects on HVC growth by reducing neuron density and enhancing early survival of new neurons recruited to HVC in females but did not significantly affect HVC volume. Conversely, DHT reduced the migration of new neurons, assessed by the expression of doublecortin, to HVC. DHT also increased syrinx mass and maintained RA (robust nucleus of the arcopallium) cytoarchitecture in the presence of aromatase inhibitors. In addition, we document the first evidence of sex-specific neuroplastic responses of the song-control system to androgens and estrogens. These findings suggest that the contributions of DHT and E2 signaling in songbird neuroplasticity may be regulated by photoperiod and that future studies should account for species and sex differences in the brain.
Background
The role played by adult neurogenesis in anxiety is not clear. A recent study revealed a surprising positive correlation between increased anxiety and elevated neurogenesis following chronic voluntary wheel running and multiple behavioural testing in mice, suggesting that adult hippocampal neurogenesis is involved in the genesis of anxiety. To exclude the possible confounding effect of multiple testing that may have occurred in the aforementioned study, we assessed (1) the effects of mouse voluntary wheel running (14 vs. 28 days) on anxiety in just one behavioural test; the open field, and (2), using different markers, proliferation, differentiation, survival and maturation of newly born neurons in the dentate gyrus immediately afterwards. Effects of wheel running on anxiety-related behaviour were confirmed in a separate batch of animals tested in another test of anxiety, the light/dark box test.
Results
Running altered measures of locomotion and exploration, but not anxiety-related behaviour in either test. 14 days running significantly increased proliferation, and differentiation and survival were increased after both running durations. 28 day running mice also exhibited an increased rate of maturation. Furthermore, there was a significant positive correlation between the amount of proliferation, but not maturation, and anxiety measures in the open field of the 28 day running mice.
Conclusions
Overall, this evidence suggests that without repeated testing, newly born mature neurons may not be involved in the genesis of anxiety per se.
The central aim of this review is to address the highly multidisciplinary topic of redox biology as related to exercise using an integrative and comparative approach rather than focusing on blood, skeletal muscle or humans. An attempt is also made to re-define 'oxidative stress' as well as to introduce the term 'alterations in redox homeostasis' to describe changes in redox homeostasis indicating oxidative stress, reductive stress or both. The literature analysis shows that the effects of non-muscle-damaging exercise and muscle-damaging exercise on redox homeostasis are completely different. Non-muscle-damaging exercise induces alterations in redox homeostasis that last a few hours post exercise, whereas muscle-damaging exercise causes alterations in redox homeostasis that may persist for and/or appear several days post exercise. Both exhaustive maximal exercise lasting only 30 s and isometric exercise lasting 1-3 min (the latter activating in addition a small muscle mass) induce systemic oxidative stress. With the necessary modifications, exercise is capable of inducing redox homeostasis alterations in all fluids, cells, tissues and organs studied so far, irrespective of strains and species. More importantly, 'exercise-induced oxidative stress' is not an 'oddity' associated with a particular type of exercise, tissue or species. Rather, oxidative stress constitutes a ubiquitous fundamental biological response to the alteration of redox homeostasis imposed by exercise. The hormesis concept could provide an interpretative framework to reconcile differences that emerge among studies in the field of exercise redox biology. Integrative and comparative approaches can help determine the interactions of key redox responses at multiple levels of biological organization.
Most non-mammalian vertebrate species add new neurons to existing brain circuits throughout life, a process thought to be essential for tissue maintenance, repair, and learning. How these new neurons migrate through the mature brain and which cues trigger their integration within a functioning circuit is not known. To address these questions, we used two-photon microscopy to image the addition of genetically labeled newly generated neurons into the brain of juvenile zebra finches. Time-lapse in vivo imaging revealed that the majority of migratory new neurons exhibited a multipolar morphology and moved in a nonlinear manner for hundreds of micrometers. Young neurons did not use radial glia or blood vessels as a migratory scaffold; instead, cells extended several motile processes in different directions and moved by somal translocation along an existing process. Neurons were observed migrating for ∼2 weeks after labeling injection. New neurons were observed to integrate in close proximity to the soma of mature neurons, a behavior that may explain the emergence of clusters of neuronal cell bodies in the adult songbird brain. These results provide direct, in vivo evidence for a wandering form of neuronal migration involved in the addition of new neurons in the postnatal brain.
In adult songbirds, neurons are continually incorporated into the telencephalic nucleus HVC (used as a proper name), a premotor region necessary for the production of learned vocalizations. Previous studies have demonstrated that neuron addition to HVC is highest when song is most variable: in juveniles during song learning, in seasonally singing adults during peaks in plasticity that precede the production of new song components, or during seasonal reestablishment of a previously learned song. These findings suggest that neuron addition provides motor flexibility for the transition from a variable song to a target song. Here we test the association between the quality of song structure and HVC neuron addition by experimentally manipulating syringeal muscle control with Botox, which produces a transient partial paralysis. We show that the quality of song structure covaries with new neuron addition to HVC. Both the magnitude of song distortion and the rate of song recovery after syringeal Botox injections were correlated with the number of new neurons incorporated into HVC. We suggest that the quality of song structure is either a cause or consequence of the number of new neurons added to HVC. Birds with naturally high rates of neuron addition may have had the greatest success in recovering song. Alternatively, or in addition, new neuron survival in the song motor pathway may be regulated by the quality of song-generated feedback as song regains its original stereotyped structure. Present results are the first to show a relationship between peripheral muscle control and adult neuron addition to cortical premotor circuits.
Environmental enrichment (EE) increases dentate gyrus (DG) neurogenesis and brain-derived neurotrophic factor (BDNF) levels. However, running is considered an element of EE. To dissociate effects of physical activity and enrichment on hippocampal neurogenesis and BDNF levels, young female C57Bl/6 mice were housed under control, running, enrichment, or enrichment plus running conditions, and injected with bromodeoxyuridine. Cell genesis was assessed after 12 d and differentiation was analyzed 1 mo later. In addition, locomotor activity in the open field and hippocampal mature BDNF peptide levels were measured. Open-field adaptation was improved in all groups, compared to controls, but more so with running. New cell proliferation, survival, neuron number, and neurotrophin levels were enhanced only when running was accessible. We conclude that exercise is the critical factor mediating increased BDNF levels and adult hippocampal neurogenesis.
It has been hypothesized that individuals who have higher demands for spatially based behaviours should show increases in hippocampal attributes. Some avian species have been shown to use a spatially based representation of their environment during migration. Further, differences in hippocampal attributes have been shown between migratory and non-migratory subspecies as well as between individuals with and without migratory experience (juveniles versus adults). We tested whether migratory behaviour might also be associated with increased hippocampal neurogenesis, and whether potential differences track previously reported differences in hippocampal attributes between a migratory (Zonotrichia leucophrys gambelii) and non-migratory subspecies (Z. l. nuttalli) of white-crowned sparrows. We found that non-migratory adults had relatively fewer numbers of immature hippocampal neurons than adult migratory birds, while adult non-migrants had a lower density of new hippocampal neurons than adult and juvenile migratory birds and juvenile non-migratory birds. Our results suggest that neurogenesis decreases with age, as juveniles, regardless of migratory status, exhibit similar and higher levels of neurogenesis than non-migratory adults. However, our results also suggest that adult migrants may either seasonally increase or maintain neurogenesis levels comparable to those found in juveniles. Our results thus suggest that migratory behaviour in adults is associated with maintained or increased neurogenesis and the differential production of new neurons may be the mechanism underpinning changes in the hippocampal architecture between adult migratory and non-migratory birds.
Both food-storing behaviour and the hippocampus change annually in food-storing birds. Food storing increases substantially in autumn and winter in chickadees and tits, jays and nutcrackers and nuthatches. The total size of the chickadee hippocampus increases in autumn and winter as does the rate of hippocampal neurogenesis. The hippocampus is necessary for accurate cache retrieval in food-storing birds and is much larger in food-storing birds than in non-storing passerines. It therefore seems probable that seasonal change in caching and seasonal change in the hippocampus are causally related. The peak in recruitment of new neurons into the hippocampus occurs before birds have completed food storing and cache retrieval for the year and may therefore be associated with spacing caches, encoding the spatial locations of caches, or creating a neuronal architecture involved in the recollection of cache sites. The factors controlling hippocampal plasticity in food-storing birds are not well understood. Photoperiodic manipulations that produce change in food-storing behaviour have no effect on either hippocampal size or neuronal recruitment. Available evidence suggests that changes in hippocampal size and neurogenesis may be a consequence of the behavioural and cognitive involvement of the hippocampus in storing and retrieving food.
The adult hippocampus in birds and mammals undergoes neurogenesis and the resulting new neurons appear to integrate structurally and functionally into the existing neural architecture. However, the factors underlying the regulation of new neuron production is still under scrutiny. In recent years, the concept that spatial memory affects adult hippocampal neurogenesis has gained acceptance, although results attempting to causally link memory use to neurogenesis remain inconclusive, possibly owing to confounds of motor activity, task difficulty or training for the task. Here, we show that ecologically relevant, spatial memory-based experiences of food caching and retrieving directly affect hippocampal neurogenesis in mountain chickadees (Poecile gambeli). We found that restricting memory experiences in captivity caused significantly lower rates of neurogenesis, as determined by doublecortin expression, compared with captive individuals provided with such experiences. However, neurogenesis rates in both groups of captive birds were still greatly lower than those in free-ranging conspecifics. These findings show that ecologically relevant spatial memory experiences can directly modulate neurogenesis, separate from other confounds that may also independently affect neurogenesis.
Aging is an important determinant of adult hippocampal neurogenesis as the proliferation of neural stem/precursor cells (NSCs) declines dramatically before middle age. Contrary to this, physical exercise is known to promote adult hippocampal neurogenesis. The objective of this study is to investigate the effects of mandatory treadmill running (TR) on neurogenesis, including 1) NSCs proliferation, 2) neurite outgrowth of neuronal progenitor cells, and 3) the survival of newborn neurons in dentate area of middle-aged animals. Compared with 3-mo-old mice, numbers of mitotic cells and neuronal progenitor cells decreased dramatically by middle age and remained at low levels after middle age. Five weeks of TR not only increased NSC proliferation and the number of immature neurons but also promoted the maturation and survival of immature neurons in middle-aged mice. The neurogenic and neurotrophic effects of TR were not due to the reduction of the age-related elevation of serum corticosterone. Significantly, 5 wk of TR restored the age-dependent decline of brain-derived neurotrophic factor and its receptor, TrkB, which are known to promote neuronal differentiation and survival. Taken together, mandatory running exercise alters the brain chemistries of middle-aged animals toward an environment that is favorable to NSC proliferation, survival, and maturation.
Dietary characteristics can modulate a bird's susceptibility to infectious challenges and subtle influences due to the level of nutrients or the types of ingredients may at times be of critical importance. This review considers seven mechanisms for nutritional modulation of resistance to infectious disease in poultry. 1) Nutrition may impact the development of the immune system, both in ovo and in the first weeks posthatch. Micronutrient deficiencies that affect developmental events, such as the seeding of lymphoid organs and clonal expansion of lymphocyte clones, can negatively impact the immune system later in life. 2) A substrate role of nutrients is necessary for the immune response so that responding cells can divide and synthesize effector molecules. The quantitative need for nutrients for supporting a normal immune system, as well as the proliferation of leukocytes and the production of antibodies during an infectious challenge, is very small relative to uses for growth or egg production. It is likely that the systemic acute phase response that accompanies most infectious challenges is a more significant consumer of nutrients than the immune system itself. 3) The low concentration of some nutrients (e.g., iron) in body fluids makes them the limiting substrates for the proliferation of invading pathogens and the supply of these nutrients is further limited during the immune response. 4) Some nutrients (e.g., fatty acids and vitamins A, D, and E) have direct regulatory actions on leukocytes by binding to intracellular receptors or by modifying the release of second messengers. 5) The diet may also have indirect regulatory effects that are mediated by the classical endocrine system. 6) Physical and chemical aspects of the diet can modify the populations of microorganisms in the gastrointestinal tract, the capacity of pathogens to attach to enterocytes, and the integrity of the intestinal epithelium.
Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.
Seasonal plasticity of structure and function is a fundamental feature of nervous systems in a wide variety of animals that occupy seasonal environments. Excellent examples of seasonal brain changes are found in the avian song control system, which has become a leading model of morphological and functional plasticity in the adult CNS. The volumes of entire brain regions that control song increase dramatically in anticipation of the breeding season. These volumetric changes are induced primarily by vernal increases in circulating sex steroids and are accompanied by increases in neuronal size, number and spacing. In several species, these structural changes in the song control circuitry are associated with seasonal changes in song production and learning. Songbirds provide important insights into the mechanisms and behavioral consequences of plasticity in the adult brain.
The high vocal center (HVC) controls song production in songbirds and sends a projection to the robust nucleus of the archistriatum (RA) of the descending vocal pathway. HVC receives new neurons in adulthood. Most of the new neurons project to RA and replace other neurons of the same kind. We show here that singing enhances mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the HVC of adult male canaries, Serinus canaria. The increased BDNF expression is proportional to the number of songs produced per unit time. Singing-induced BDNF expression in HVC occurs mainly in the RA-projecting neurons. Neuronal survival was compared among birds that did or did not sing during days 31-38 after BrdUrd injection. Survival of new HVC neurons is greater in the singing birds than in the nonsinging birds. A positive causal link between pathway use, neurotrophin expression, and new neuron survival may be common among systems that recruit new neurons in adulthood.
We have previously reported the presence of dying cells in the granule cell layer (GCL) of adult rat dentate gyrus (DG), where neurogenesis occurs. In particular, we found that cell death in the GCL increased in vitamin E deficiency and decreased in vitamin E supplementation. These findings were regarded as related to changes in neurogenesis rate, which in turn was influenced by vitamin E availability; a neuroprotective effect of vitamin E on cell death was also proposed. In order to verify this latter hypothesis, we have studied cell death in all layers of DG in vitamin E-deficient and vitamin E-supplemented rats and in control rats at different ages, using TUNEL and nick translation techniques. The phenotype of TUNEL-positive cells was characterized and the existence of dying BrdU-positive cells was investigated. Dying cells with neuronal phenotype were observed throughout the DG in all experimental groups. The number of TUNEL-positive cells decreased from juvenile to adult age. A higher number of TUNEL-positive cells in vitamin E-deficient rats and a lower number in vitamin E-supplemented rats, with respect to age-matched controls, were found; moreover, in these groups, TUNEL-positive cells had a different percentage distribution in the different layers of the DG. Our results confirm the occurrence of cell death in DG, demonstrate that cell death affects neuronal cells and support the hypothesis that the effect of vitamin E on cell death is not related to neurogenesis.
In seasonally breeding songbirds, variations in testosterone and song correlate with volume changes in brain nuclei associated with song, including the HVC. The authors tested whether singing can lead to activity-dependent increases in HVC volume by examining song output in starlings (Sturnus vulgaris). The authors manipulated males' environments so that only some were dominant with nestboxes, whereas others were not. Some of these males thus sang at higher rates and had larger HVC volume than others. The study was conducted over 2 years. In 1 year, males selectively occupied nestboxes but did not sing. HVC volume did not differ in these starlings, indicating that nestbox possession alone cannot increase HVC. The findings suggest that changes in song nuclei volume can be driven by changes in singing.
Omega-3 fatty acids play crucial roles in the development and function of the central nervous system. These components, which must be obtained from dietary sources, have been implicated in a variety of neurodevelopmental and psychiatric disorders. Furthermore, the presence of omega-6 fatty acids may interfere with omega-3 fatty acid metabolism. The present study investigated whether changes in dietary ratios of omega-3:omega-6 fatty acids influence neurogenesis in the lobster (Homarus americanus) brain where, as in many vertebrate species, neurogenesis persists throughout life. The factors that regulate adult neurogenesis are highly conserved among species, and the crustacean brain has been successfully utilized as a model for investigating this process. In this study, lobsters were fed one of three diets that differed in fatty acid content. These animals were subsequently incubated in 5-bromo-2'-deoxyuridine (BrdU) to detect cells in S-phase of the cell cycle. A quantitative analysis of the resulting BrdU-labeled cells in the projection neuron cluster in the brain shows that short-term augmentation of dietary omega-3 relative to omega-6 fatty acids results in significant increases in the numbers of S phase cells, and that the circadian pattern of neurogenesis is also altered. It is proposed that the ratio of omega-3:omega-6 fatty acids may alter neurogenesis via modulatory influences on membrane proteins, cytokines and/or neurotrophins.
Post-embryonic neurogenesis is a fundamental feature of the vertebrate brain. However, the level of adult neurogenesis decreases significantly with phylogeny. In the first part of this review, a comparative analysis of adult neurogenesis and its putative roles in vertebrates are discussed. Adult neurogenesis in mammals is restricted to two telencephalic constitutively active zones. On the contrary, non-mammalian vertebrates display a considerable amount of adult neurogenesis in many brain regions. The phylogenetic differences in adult neurogenesis are poorly understood. However, a common feature of vertebrates (fish, amphibians and reptiles) that display a widespread adult neurogenesis is the substantial post-embryonic brain growth in contrast to birds and mammals. It is probable that the adult neurogenesis in fish, frogs and reptiles is related to the coordinated growth of sensory systems and corresponding sensory brain regions. Likewise, neurons are substantially added to the olfactory bulb in smell-oriented mammals in contrast to more visually oriented primates and songbirds, where much fewer neurons are added to the olfactory bulb. The second part of this review focuses on the differences in brain plasticity and regeneration in vertebrates. Interestingly, several recent studies show that neurogenesis is suppressed in the adult mammalian brain. In mammals, neurogenesis can be induced in the constitutively neurogenic brain regions as well as ectopically in response to injury, disease or experimental manipulations. Furthermore, multipotent progenitor cells can be isolated and differentiated in vitro from several otherwise silent regions of the mammalian brain. This indicates that the potential to recruit or generate neurons in non-neurogenic brain areas is not completely lost in mammals. The level of adult neurogenesis in vertebrates correlates with the capacity to regenerate injury, for example fish and amphibians exhibit the most widespread adult neurogenesis and also the greatest capacity to regenerate central nervous system injuries. Studying these phenomena in non-mammalian vertebrates may greatly increase our understanding of the mechanisms underlying regeneration and adult neurogenesis. Understanding mechanisms that regulate endogenous proliferation and neurogenic permissiveness in the adult brain is of great significance in therapeutical approaches for brain injury and disease.
The invention of a novel analytical technique often helps to launch a new science. What microscopes were for the emergence of cell biology as a discipline, or the cathode-ray oscilloscope for neurophysiology, it was the sound spectrograph that, immediately after the Second World War, enabled the birth of the science of birdsong. There had been no lack of interest in birdsong previously, and fascinating and important discoveries were made, especially about the functions of song. But never before had researchers come together to form a coherent discipline. Until about 1950, everyone interested in birdsong had no choice but to work by ear. Only when the sound spectrograph became available was it possible, for the first time, to grapple objectively with the daunting variability of birdsong, and to specify its structure precisely. Almost immediately a multitude of new issues became accessible for scientific scrutiny and experimentation.
Sturnus vulgaris diets were composed mainly of animal matter (64%) early in the postbreeding roosting season (June-July) when roosting flocks were small and numerous. Later in the season, animal foods were replaced by plant materials when small roosts coalesced into fewer but larger roosting flocks. The change in diet corresponded to changes in the pattern of roosting behavior. One major benefit of roosting may be in providing access to plant foods that can be efficiently exploited during the morning and evening commutes from and to the roost.-from Authors
Neurogenesis occurs throughout adult life in rat dentate gyrus. Factors and mechanisms of adult neurogenesis regulation are not well known. Vitamin E deficiency has been found to deliver a neurogenetic potential in rat dorsal root ganglia. To determine whether the role of tocopherols in adult neurogenesis may be generalized to the central nervous system, changes in adult rat dentate gyrus neurogenesis were investigated in vitamin E deficiency. Neurogenesis was quantitatively studied by determination of the density of 5-bromo-2′-deoxyuridine (BrdU)-labeled cells and by determination of the total number of cells in the granule cell layer. The BrdU-labeled cells were immunocytochemically characterized by demonstration of neuronal marker calbindin D28K. The following results were found: (1) the volume of the granule layer increased in controls from 1 to 5 months of age, mainly due to cell density decrease; (2) the volume increased by a similar amount in vitamin E–deficient rats, mainly because of an increase in cell number; (3) BrdU-positive cells were more numerous in vitamin E–deficient rats in comparison to age-matched controls; (4) the increase in proliferated cells was located in the hilus and in the plexiform layer. This study confirms that neurogenesis occurs within adult dentate gyrus and demonstrates that this process is enhanced in vitamin E deficiency. This finding indicates that vitamin E may be an exogenous factor regulating adult neurogenesis. J. Comp. Neurol. 411:495–502, 1999. © 1999 Wiley-Liss, Inc.
Although fat is the primary fuel for migratory flight in birds, protein is also used. Catabolism of tissue protein yields
five times as much water per kilojoule as fat, and so one proposed function of protein catabolism is to maintain water balance
during nonstop flights. To test the protein-for-water hypothesis, we flew Swainson’s thrushes (Catharus ustulatus) in a climatic wind tunnel under high- and low-humidity conditions at 18°C for up to 5 hours. Flight under dry conditions
increased the rates of lean mass loss and endogenous water production and also increased plasma uric acid concentration. These
data demonstrate that atmospheric humidity influences fuel composition in flight and suggest that protein deposition and catabolism
during migration are, in part, a metabolic strategy to maintain osmotic homeostasis during flight.
Adult neural stem cells in the dentate gyrus of the hippocampus are negatively and positively regulated by a broad range of environmental stimuli that include aging, stress, social interaction, physical activity, and dietary modulation. Interestingly, dietary regulation has a distinct outcome, such that reduced dietary intake enhances neurogenesis, whereas excess calorie intake by a high-fat diet has a negative effect. As a type of metabolic stress, dietary restriction (DR) is also known to extend life span and increase resistance to age-related neurodegenerative diseases. However, the potential application of DR as a "neurogenic enhancer" in humans remains problematic because of the severity of restriction and the protracted duration of the treatment required. Therefore, the authors consider that an understanding of the neurogenic mechanisms of DR would provide a basis for the identification of the pharmacological and nutraceutical interventions that mimic the beneficial effects of DR without limiting caloric intake. The current review describes the regulatory effect of DR on hippocampal neurogenesis and presents a possible neurogenic mechanism.
Chronic elevations in glucocorticoids can decrease the production and survival of new cells in the adult brain. In rat hippocampus, supraphysiological doses of dehydroepiandrosterone (DHEA; a sex steroid precursor synthesized in the gonads, adrenals, and brain) have antiglucocorticoid properties. With male song sparrows (Melospiza melodia), we examined the effects of physiological doses of corticosterone, the primary circulating glucocorticoid in birds, and DHEA on adult neuroplasticity. We treated four groups of nonbreeding sparrows for 28 days with empty (control), corticosterone, DHEA, or corticosterone + DHEA implants. Subjects were injected with BrdU on days 3 and 4. In HVC, a critical song control nucleus, corticosterone and DHEA had independent, additive effects. Corticosterone decreased, whereas DHEA increased, HVC volume, NeuN(+) cell number, and BrdU(+) cell number. Coadministration of DHEA completely reversed the neurodegenerative effects of chronic corticosterone treatment. In an efferent target of HVC, the robust nucleus of the arcopallium (RA), DHEA increased RA volume, but this effect was blocked by coadministration of corticosterone. There were similar antagonistic interactions between corticosterone and DHEA on BrdU(+) cell number in the hippocampus and ventricular zone. This is the first report on the effects of corticosterone treatment on the adult song control circuit, and HVC was the most corticosterone-sensitive song nucleus examined. In HVC, DHEA is neuroprotective and counteracts several pronounced effects of corticosterone. Within brain regions that are particularly vulnerable to corticosterone, such as the songbird HVC and rat hippocampus, DHEA appears to be a potent native antiglucocorticoid.
Brain plasticity and adult neurogenesis may play a role in many ecologically important processes including mate recognition, song learning and production, and spatial memory processing. In a number of species, both physical and social environments appear to influence attributes (e.g., volume, neuron number, and neurogenesis) of particular brain regions. The hippocampus in particular is well known to be especially sensitive to such changes. Although social grouping in many taxa includes the formation of male and female pairs, most studies of the relationship between social environment and the hippocampus have typically considered only solitary animals and those living in same-sex groups. Thus, the aim of this study was to compare the volume of the hippocampal formation, the total number of hippocampal neurons, and the number of immature neurons in the hippocampus (as determined by doublecortin expression) in mountain chickadees (Poecile gambeli) housed in groups of males and females, male-female pairs, same sex pairs of either males or females, and as solitary individuals. The different groups were visually and physically, but not acoustically, isolated from each other. We found no significant differences between any of our groups in hippocampal volume, the total number of hippocampal neurons, or the number of immature neurons. Our results thus provided no support to the hypothesis that social group composition and/or size have an effect on hippocampal morphology and neurogenesis.
Neuron recruitment has been implicated in morphological and functional plasticity in the adult brain. Whereas mammals restrict neuron recruitment specifically to two regions of known plasticity, the hippocampus and olfactory bulb, newborn neurons are found throughout the forebrain of adult songbirds. In order to study the area-specificity of the widespread proliferation and recruitment in the songbird brain, six adult male canaries received repetitive intraperitoneal injections of the mitotic marker BrdU (5-bromo-2-deoxyuridine) and were sacrificed after 24 hours to study proliferation or after 38 days to study recruitment. Migration and incorporation of new neurons was apparent throughout many but not all parts of the canary forebrain and was quantitatively related to mitotic levels in the most closely associated proliferative zones. Surprisingly, some areas of the vocal control system sensitive to plastic changes, such as nucleus higher vocal center (HVC) and area X, recruited similar numbers of new neurons as their surrounding brain tissues, employing no specific directional mechanisms. The distribution pattern in and around HVC could best be described by a random displacement model, where cells originating from the overlying lateral ventricle can move independently in any direction. Other plastic song control areas, such as the medial magnocellular nucleus of anterior nidopallium and the robust nucleus of arcopallium, were specifically avoided by migrating neurons, while migration toward the olfactory bulb showed high specificity, similar to the mammalian rostral migratory stream. Thus, different mechanisms appear to organize area-specific neuron recruitment in different recipients of the adult songbird brain, unrelated to global plasticity of brain regions.
Neurogenesis occurs throughout adult life in rat dentate gyrus. Factors and mechanisms of adult neurogenesis regulation are not well known. Vitamin E deficiency has been found to deliver a neurogenetic potential in rat dorsal root ganglia. To determine whether the role of tocopherols in adult neurogenesis may be generalized to the central nervous system, changes in adult rat dentate gyrus neurogenesis were investigated in vitamin E deficiency. Neurogenesis was quantitatively studied by determination of the density of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells and by determination of the total number of cells in the granule cell layer. The BrdU-labeled cells were immunocytochemically characterized by demonstration of neuronal marker calbindin D28K. The following results were found: (1) the volume of the granule layer increased in controls from 1 to 5 months of age, mainly due to cell density decrease; (2) the volume increased by a similar amount in vitamin E-deficient rats, mainly because of an increase in cell number; (3) BrdU-positive cells were more numerous in vitamin E-deficient rats in comparison to age-matched controls; (4) the increase in proliferated cells was located in the hilus and in the plexiform layer. This study confirms that neurogenesis occurs within adult dentate gyrus and demonstrates that this process is enhanced in vitamin E deficiency. This finding indicates that vitamin E may be an exogenous factor regulating adult neurogenesis.
The waning and waxing of neurogenesis in brain areas such as the dentate gyrus is proposed as a key factor in the descent into and recovery from clinical depression, respectively. A decrease in neurogenesis could occur due to genetic factors, stress (especially because of the involvement of adrenal corticoids), and/or a decline in serotonergic neurotransmission. An increase in neurogenesis could be brought about by several factors, but especially those that activate the serotonin 5-HT(1A) receptor. The possible interaction of immune system factors, especially the proinflammatory cytokines, with adult brain neurogenesis is discussed.
Exposure to an enriched environment and physical activity, such as voluntary running, increases neurogenesis of granule cells in the dentate gyrus of adult mice. These stimuli are also known to improve performance in hippocampus-dependent learning tasks, but it is unclear whether their effects on neurogenesis are exclusive to the hippocampal formation. In this study, we housed adult mice under three conditions (enriched environment, voluntary wheel running and standard housing), and analysed proliferation in the lateral ventricle wall and granule cell neurogenesis in the olfactory bulb in comparison to the dentate gyrus. Using bromodeoxyuridine to label dividing cells, we could not detect any difference in the number of newly generated cells in the ventricle wall. When giving the new cells time to migrate and differentiate in the olfactory bulb, we observed no changes in the number of adult-generated olfactory granule cells; however, voluntary running and enrichment produced a doubling in the amount of new hippocampal granule cells. The discrepancy between the olfactory bulb and the dentate gyrus suggests that these living conditions trigger locally through an as yet unidentified mechanism specific to neurogenic signals in the dentate gyrus.
Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions.
Environmental enrichment (EE) and voluntary exercise (VEx) have consistently been shown to increase adult hippocampal neurogenesis and improve spatial learning ability. Although it appears that these two manipulations are equivalent in this regard, evidence exists that EE and VEx affect different phases of the neurogenic process in distinct ways. We review the data suggesting that EE increases the likelihood of survival of new cells, whereas VEx increases the level of proliferation of progenitor cells. We then outline the factors that may mediate these relationships. Finally, we provide a model showing that VEx leads to the convergence of key somatic and cerebral factors in the dentate gyrus (DG) to induce cell proliferation. Although insufficient evidence exists to provide a similar model for EE, we suggest that EE-induced cell survival in the DG involves cortical restructuring as a means of promoting survival. We conclude that EE and VEx lead to an increase in overall hippocampal neurogenesis via dissociable pathways, and should therefore, be considered distinct interventions with regard to hippocampal plasticity and associated behaviors.
Docosahexaenoic acid (22:6n-3), one of the main structural lipids in the mammalian brain, plays crucial roles in the development and function of brain neurons. We examined the effect of docosahexaenoic acid on neuronal differentiation of neural stem cells in vitro and in vivo. Neural stem cells obtained from 15.5-day-old rat embryos were propagated as neurospheres and cultured under differential conditions with or without docosahexaenoic acid for 4 and 7 days. Docosahexaenoic acid significantly increased the number of Tuj1-positive neurons compared with the control on both culture days, and the newborn neurons in the docosahexaenoic acid group were morphologically more mature than in the control. Docosahexaenoic acid significantly decreased the incorporation ratio of 5-bromo-2'-deoxyuridine, the mitotic division marker, during the first 24 h period; it also significantly decreased the number of pyknotic cells on day 7. Thus, docosahexaenoic acid promotes the differentiation of neural stem cells into neurons by promoting cell cycle exit and suppressing cell death. Furthermore, dietary administration of docosahexaenoic acid significantly increased the number of 5-bromo-2'-deoxyuridine(+)/NeuN(+) newborn neurons in the granule cell layer of the dentate gyrus in adult rats. These results demonstrate that docosahexaenoic acid effectively promotes neurogenesis both in vitro and in vivo, suggesting that it has the new property of modulating hippocampal function regulated by neurogenesis.
Vitamin E is essential for neurological function. This fact, together with a growing body of evidence indicating that neurodegenerative processes are associated with oxidative stress, lead to the convincing idea that several neurological disorders may be prevented and/or cured by the antioxidant properties of vitamin E. In this review, some aspects related to the role of vitamin E against Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and ataxia with vitamin E deficiency will be presented.
The protein doublecortin (DCX) is expressed in post-mitotic migrating and differentiating neurons in the developing vertebrate brain and, as a part of the microtubule machinery, is required for neuronal migration. DCX expression is generally maximal during embryonic and early post-natal life but decreases markedly and almost disappears in older animals in parallel with the major decrease or cessation of neurogenesis. In several seasonally breeding songbird species such as canaries, the volume of several song control nuclei in the brain varies seasonally such that the largest nuclei are observed in the late spring and early summer. This variation is based on changes in cell size, dendritic branching, and, in nucleus HVC, on the incorporation of neurons newly born in adulthood. Because songbirds maintain an active neurogenesis and neuronal incorporation in their telencephalon throughout their lives, we investigated here the distribution of DCX-immunoreactive (ir) structures in the brain of adult male canaries. Densely stained DCX-ir cells were found exclusively in parts of the telencephalon that are known to incorporate new neurons in adulthood, in particular the nidopallium. Within this brain region, the boundaries of the song control nucleus HVC could be clearly distinguished from surrounding structures by a higher density of DCX-ir structures. In most telencephalic areas, about two thirds of these cells displayed a uni- or bipolar fusiform morphology suggesting they were migrating neurons. The rest of the DCX-ir cells in the telencephalon were larger and had a round multipolar morphology. No such staining was found in the rest of the brain. The broad expression of DCX specifically in adult brain structures that exhibit the characteristic of active incorporation of new neurons suggests that DCX plays a key role in the migration of new neurons in the brain of adult songbirds as it presumably does during ontogeny.
Adult neurogenesis is often correlated with learning new tasks, suggesting that a function of incorporating new neurons is to permit new memory formation. However, in the zebra finch, neurons are added to the song motor pathway throughout life, long after the initial song motor pattern is acquired by about 3 months of age. To explore this paradox, we examined the relationship between adult song structure and neuron addition using sensitive measures of song acoustic structure. We report that between 4 and 15 months of age there was an increase in the stereotypy of fine-grained spectral and temporal features of syllable acoustic structure. These results indicate that the zebra finch continues to refine motor output, perhaps by practice, over a protracted period beyond the time when song is first learned. Over the same age range, there was a decrease in the addition of new neurons to HVC, a region necessary for song production, but not to Area X or the hippocampus, regions not essential for singing. We propose that age-related changes in the stereotypy of syllable acoustic structure and HVC neuron addition are functionally related.
This article provides an overview of our understanding of life-long neurogenesis in the decapod crustacean brain, where the proliferation of sensory and interneurons is controlled by many of the same factors as is neurogenesis in the mammalian brain. The relative simplicity, spatial organization and accessibility of the crustacean brain provide opportunities to examine specific neuronal pathways that regulate neurogenesis and the sequence of gene expression that leads to neuronal differentiation.
Research in humans and animals has shown that exercise improves mood and cognition. Physical activity also causes a robust increase in neurogenesis in the dentate gyrus of the hippocampus, a brain area important for learning and memory. The positive correlation between running and neurogenesis has raised the hypothesis that the new hippocampal neurons may mediate, in part, improved learning associated with exercise. The present review gives an overview of research pertaining to exercise-induced cell genesis, its possible relevance to memory function and the cellular mechanisms that may be involved in this process.
It is established that in songbirds the size of several brain song control nuclei varies seasonally, based on changes in cell size, dendritic branching and, in nucleus HVC, the incorporation of newborn neurons. In the developing and adult mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic neurons and, as a part of the microtubule machinery, required for neuronal migration. We recently showed that in adult canaries, DCX-immunoreactive (ir) cells are present throughout the telencephalon, but the link between DCX and the active neurogenesis observed in songbirds remained uncertain. We demonstrate here that DCX labels recently born cells in the canary telencephalon and that, in parallel with changes in HVC volume, the number of DCX-ir cells is increased specifically in the HVC of testosterone-treated males compared with castrates, and in castrated testosterone-treated males paired with a female as compared with males paired with another male. The numbers of elongated DCX-ir cells (presumptive migrating neurons) and round multipolar DCX-ir cells (differentiating neurons) were also affected by the sex of the subjects and their photoperiodic condition (photosensitive vs photostimulated vs photorefractory). Thus, in canaries the endocrine state, as well as the social or photoperiodic condition independently of variation in steroid hormone action, affects the number of cells expressing a protein involved in neuronal migration specifically in brain areas that incorporate new neurons in the telencephalon. The DCX gene may be one of the targets by which testosterone and social stimuli induce seasonal changes in the volume of song nuclei.
- M L Scott
- M C Nesheim
- R J Young
Scott, M.L., Nesheim, M.C. & Young, R.J. (1982) Nutrition of the Chicken.
M.L. Scott & Associates, Ithaca, NY.
Docosahexaenoic acid promotes neurogenesis in vitro and in vivo
- Kawakita
Seasonal plasticity in the adult brain
- Tramontin