Exercise enhances learning and hippocampal neurogenesis in aged mice

Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2005; 25(38):8680-5. DOI: 10.1523/JNEUROSCI.1731-05.2005
Source: PubMed


Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel running would benefit mice that were sedentary until 19 months of age. Specifically, young and aged mice were housed with or without a running wheel and injected with bromodeoxyuridine or retrovirus to label newborn cells. After 1 month, learning was tested in the Morris water maze. Aged runners showed faster acquisition and better retention of the maze than age-matched controls. The decline in neurogenesis in aged mice was reversed to 50% of young control levels by running. Moreover, fine morphology of new neurons did not differ between young and aged runners, indicating that the initial maturation of newborn neurons was not affected by aging. Thus, voluntary exercise ameliorates some of the deleterious morphological and behavioral consequences of aging.

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    • "MRI studies have demonstrated an increase in cortical grey and white matter volume in response to exercise programs (Chaddock et al., 2010; Erickson et al., 2009, 2011). Additionally, Colcombe et al. (2004) have indicated that high cardiovascular fitness (measured both cross-sectionally and after a 12-month increase in memory performance (O'Callaghan, Ohle, & Kelly, 2007; van Praag, Christie, Sejnowski, & Gage, 1999) as well as Hebbian LTP (Farmer et al., 2004; O'Callaghan, et al., 2007; van Praag et al., 1999, 2005). However, due to the invasive nature of the above procedures, to date few in vivo human studies have been conducted, limiting our understanding of the relationship between physical activity and LTP in the human brain. "
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    ABSTRACT: A growing body of literature has explored the influence of physical activity on brain structure and function. While the mechanisms of this relationship remain largely speculative, recent research suggests that one of the effects of physical exercise is an increase in synaptic long-term potentiation (LTP). This has not yet been explored directly in humans due to the difficulty of measuring LTP non-invasively. However, we have previously established that LTP- like changes in visual-evoked potentials (VEPs) can be measured in humans. Here, we investigated whether physical fitness status affects the degree of visual sensory LTP. Using a self-report measure of physical activity, participants were split into two groups: a high-activity group, and a low-activity group. LTP was measured and compared between the two groups using the previously established electroencephalography-LTP paradigm, which assesses the degree to which the N1b component of the VEP elicited by a sine grating is potentiated (enhanced) following a rapid “tetanic” presentation of that grating. Both groups demonstrated increased negativity in the amplitude of the N1b component of the VEP immediately after presentation of the visual “tetanus,” indicating potentiation. However, after a 30-min rest period, the N1b for the high-activity group remained potentiated while the N1b for the low-activity group returned to baseline. This study presents the first evidence for the impact of self-reported levels of physical activity on LTP in humans, and sheds light on potential neurological mechanisms underlying the relationship between physical fitness and cognition. ( JINS , 2015, 21 , 831–840)
    Journal of the International Neuropsychological Society 11/2015; 21(10):831-840. DOI:10.1017/S1355617715001095 · 2.96 Impact Factor
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    • "Chronic exercise exerts a beneficial impact on cognitive impairment. Long-term voluntary or treadmill running improved memory performance, enhanced hippocampal neurogenesis, and strengthened long-term potentiation in aged rodents [13] [14]. In addition, the 21 consecutive days of restraint stress led to cognitive decline and augmented hippocampal oxidative damage, which were reversed by treadmill running for 12 weeks [15]. "
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    ABSTRACT: The present study demonstrates that prolonged restraint administration for 21 days caused memory impairment and induced hippocampal endoplasmic reticulum (ER) stress-mediated apoptosis. On the contrary, this change was revered by treadmill running for 8 weeks. Repeated psychological stress caused an increase in escape latency time in the water maze test, accompanied by the induction of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and cleaved/active caspase-12 protein in the hippocampus. The expression pattern of ER stress response-related proteins were counter-regulated by chronic exercise, as indicated by a reduction in GRP78, CHOP, and cleaved caspase-12, along with a decrease in escape latency time. In addition, the hippocampal expression pattern of phospho-cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) opposed that of ER stress response components. Accordingly, chronic exercise may attenuate prolonged stress-induced hippocampal ER stress and memory deficit, likely through CREB/BDNF signaling.
    11/2015; 19(3):191-7. DOI:10.5717/jenb.2015.15080705
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    • "As such, environmental enrichment paradigms provide a promising avenue for investigators to assess the effects of a stimulating environment on the brain both during homeostasis and during recovery from disease states. While environmental enrichment is known to influence hippocampal neurogenesis (reviewed in Nithianantharajah and Hannan, 2006; Van Praag et al., 2000), the scope of the current article is oligodendrocyte lineage cellular dynamics. "
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    ABSTRACT: Many behavioral experiences are known to promote hippocampal neurogenesis. In contrast, the ability of behavioral experiences to influence the production of oligodendrocytes and myelin sheath formation remains relatively unknown. However, several recent studies indicate that voluntary exercise and environmental enrichment can positively influence both oligodendrogenesis and myelination, and that, in contrast, social isolation can negatively influence myelination. In this review we summarize studies addressing the influence of behavioral experiences on oligodendrocyte lineage cells and myelin, and highlight potential mechanisms including experience-dependent neuronal activity, metabolites, and stress effectors, as well as both local and systemic secreted factors. Although more study is required to better understand the underlying mechanisms by which behavioral experiences regulate oligodendrocyte lineage cells, this exciting and newly emerging field has already revealed that oligodendrocytes and their progenitors are highly responsive to behavioral experiences and suggest the existence of a complex network of reciprocal interactions among oligodendrocyte lineage development, behavioral experiences, and brain function. Achieving a better understanding of these relationships may have profound implications for human health, and in particular, for our understanding of changes in brain function that occur in response to experiences.
    Neuropharmacology 09/2015; DOI:10.1016/j.neuropharm.2015.09.016 · 5.11 Impact Factor
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