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Central administration of neuropeptide Y reduces the cellular heat stress response and may enhance spleen antioxidative functions in heat-exposed chicks
Abstract
Previously it was found that mRNA expression of neuropeptide Y (NPY) was increased in the chicken brain under heat stress. NPY has also been reported as an anti-stress factor to regulate brain functions in heat exposed chicks. However, to the best of our knowledge, there is no report on the action of central NPY in the immune organs under heat stress. The aim of this study was to examine whether central injection of NPY can regulate heat stress response in the spleen and liver. After intracerebroventricular (ICV) injection of NPY, chicks were exposed to control thermoneutral temperature (CT: 30 ± 1°C) or high ambient temperature (HT: 35 ± 1°C) chambers for 60 min. Central injection of NPY caused lowering in rectal temperature under CT, but not under HT. Moreover, ICV injection of NPY caused a significant lower mRNA expression of heat-shock protein-70 and higher expression of glutathione synthase in the spleen, but not liver. Furthermore, plasma uric acid concentrations were significantly increased by the ICV injection of NPY in chicks under HT. These results indicate that brain NPY may contribute to attenuate the intracellular heat stress response and enhance antioxidative status in the immune organ, spleen in chicks.
... Rectal temperature was measured using a digital thermometer with an accuracy of ±0.1 • C (Thermalert TH-5, Physitemp Instruments Inc., USA). The thermistor probe was inserted into the colon (rectum) through the cloaca to a depth of 2 cm as reported previously Chowdhury et al., 2015;Eltahan et al., 2017;Bahry et al., 2017;Nishimura et al., 2022). At the end of 3 h exposure to HT for both acute and chronic heat challenge, all chicks were immediately euthanized for culling by exposure to isoflurane (Mylan Inc., Tokyo, Japan). ...
... In Experiment 3, feeding and acclimatization of chicks were similar as describe above in Experiment 2. On the day of the experiment, chicks (6 days old; n = 12 per group) were intracerebroventricularly injected with 10 μL of either 0 or 1 nmol NPY. The dose was chosen based on our previous studies where 375 pmol reduced body temperature under CT but not under HT Nishimura et al., 2022). Therefore, we considered that a higher dose (1 nmol) may be more effective under HT. ...
High ambient temperatures (HT) can increase diencephalic neuropeptide Y (NPY) expression, and central injection of NPY attenuates heat stress responses while inducing an antioxidative state in the chick spleen. However, there is a lack of knowledge about NPY receptor expression, and its regulation by HT, in the chick spleen. In the current study, male chicks were used to measure the expression of NPY receptors in the spleen and other immune organs under acute (30 vs. 40 ± 1℃ for 3 h) or chronic (30 vs. 40 ± 1℃ for 3 h/day for 3 days) exposure to HT and in response to central injection of NPY (47 pmol, 188 pmol, or 1 nmol). We found that NPY-Y4 receptor mRNA was expressed in the spleen, but not in other immune organs studied. Immunofluorescence staining revealed that NPY-Y4 receptors were localized in the splenic pulp. Furthermore, NPY-Y4 receptor mRNA increased in the chick spleen under both acute and chronic exposure to HT. Central NPY at two dose levels (47 and 188 pmol) and a higher dose (1 nmol) did not increase splenic NPY-Y4 receptor mRNA expression or splenic epinephrine under HT (35 ± 1℃), and significantly increased 3-methoxy-4-hydroxyphenylglycol (MHPG) concentrations under HT (40 ± 1℃). In conclusion, increased expression of NPY-Y4 receptor mRNA in the spleen under HT suggests that Y4 receptor may play physiological roles in response to HT in male chicks.
... NPY typically is orexigenic and related to the onset of puberty in birds (Fraley and Kuenzel, 1993). NPY is released under stress to increase food intake to use as energy and acts to decrease corticosterone by inhibiting CRH to minimize the stress response (Bahry et al., 2017;Nishimura et al., 2022). Centrally administered NPY in heat stressed broiler chicks decreased plasma corticosterone via direct inhibition of CRH (Bahry et al., 2017). ...
Previous studies from our lab suggest that transportation of early adulthood ducks can have long lasting physiological effects. To better understand how transportation affects the ducks’ physiology, we evaluated several central and peripheral parameters. Thirty-six, 23-week-old ducks were collected at a commercial breeder facility and randomly assigned to one of three treatment groups (n = 6/sex/treatment): 1) caught and euthanized (control), 2) caught and put in a crated in the pen for 90 min (crate), or 3) caught, crated, and transported in a truck for 90 min (transport) to simulate actual transportation. Blood was collected for serum corticosterone and blood smear analyses. Brains were hemisected and each half was dissected into three brain areas: caudal mesencephalon (CM), rostral mesencephalon (RM), and diencephalon (DI). Mass spectrometry was run on the right half of the brain, and gene expression of TPH1, TPH2, TH, CRH, and NPY were measured on the left half of brain using qRT-PCR. Serum corticosterone levels were increased (p = 0.01) in crated hens and in transported hens and drakes (p = 0.0084) when compared to control. HLR was increased (p = 0.035) in crated hens and transported hens and drakes compared to control. No differences in serotonin turnover were observed in drakes but increased in hens within the CM and RM from control to crate (p = 0.01) and crate to transport (p = 0.016). There were no differences in DA turnover or in gene expression for all brain areas for drakes and CM and RM for hens. Within the DI, hens showed a decrease (p = 0.03) in TPH1 for transport compared to crate. Overall, transportation elicits an acutely stressful event that increases corticosterone and HLR in a sex dependent manner where hens appear to be more reactive to the stressor than drakes. Our data supports that when assessing a stress response, care must be given to the sex of the bird and to the relative timepoint of sampling compared to the perceived onset of the stressor.
The impact of heat stress (HS) on production is intricately linked with feed intake. We investigated the effects of HS on intestines and diencephalic genes in Pekin ducks. One hundred and sixty adult ducks were allocated to two treatment rooms. The control room was maintained at 22°C and the HS room at 35°C for the first 10 h of the day then reduced to 29.5°C. After 3 weeks, 10 hens and 5 drakes were euthanized from each room and jejunum and ileum collected for histology. Brains were collected for gene expression analysis using qRT‐PCR. Intestinal morphology data were analyzed with two‐way ANOVA and diencephalic gene data were analyzed with Kruskal–Wallis test. There was an increase in villi width in the ileum ( p = .0136) and jejunum ( p = .0019) of HS hens compared to controls. HS drakes showed a higher crypt depth (CD) in the jejunum ( p = .0198) compared to controls. There was an increase in crypt goblet cells (GC) count in the ileum ( p = .0169) of HS drakes compared to HS hens. There was higher villi GC count ( p = .07) in the jejunum of HS drakes compared to controls. There was an increase in the crypt GC density ( p = .0054) in the ileum, not jejunum, of HS drakes compared to HS hens. Further, there were no differences in the proopiomelanocortin gene expression in either sex but there was an increase in the expression of neuropeptide Y (NPY) gene in HS hens ( p = .031) only and a decrease in the corticotropin releasing hormone gene in the HS drakes ( p = .037) compared to controls. These data show that there are sex differences in the effect of HS on gut morphology while the upregulation in NPY gene may suggest a role in mediating response to chronic HS.
Due to their high specificity toward the target and their low toxicity, biological drugs have been successfully employed in a wide range of therapeutic areas. It is yet to be mentioned that biologics exhibit unfavorable pharmacokinetic properties, are susceptible to degradation by endogenous enzymes, and cannot penetrate biological barriers such as the blood–brain barrier (i.e., the major impediment to reaching the central nervous system (CNS)). Attempts to overcome these issues have been made by exploiting the intracerebroventricular and intrathecal routes of administration. The invasiveness and impracticality of these procedures has, however, prompted the development of novel drug delivery strategies including the intranasal route of administration. This represents a non-invasive way to achieve the CNS, reducing systemic exposure. Nonetheless, biotherapeutics strive to penetrate the nasal epithelium, raising the possibility that direct delivery to the nervous system may not be straightforward. To maximize the advantages of the intranasal route, new approaches have been proposed including the use of cell-penetrating peptides (CPPs) and CPP-functionalized nanosystems. This review aims at describing the most impactful attempts in using CPPs as carriers for the nose-to-brain delivery of biologics by analyzing their positive and negative aspects.
Phyllanthus amarus has been exploited for the management of several aliments in folkloric medicine. The present study therefore investigates the restorative potential of its leaves extract on hepatic and renal assault induced by CCl4 and rifampicin respectively. Eight groups (I-VIII) containing five animals each were created for the experiments. Group I were fed with normal commercial pellet only, while group II were exposed to single intraperitoneal injection of 3 ml/kg b.w. of CCl4 only. Groups III, IV and V animals were administered 3 ml/kg b/w of CCl4 and treated with 50, 100 mg/kg b. w. of P. amarus and 100 mg/kg b.w of silymarin respectively. Group VI animals were orally exposed to 250 mg/kg b/w of rifampicin only while groups VII and VIII were treated with 50 and 100 mg/kg b. w. P. amarus respectively for 14 days after the initial exposure to 250 mg/kg b/w rifampicin . Liver and kidney function tests such as alanine amino transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, urea and uric acid were determined in the serum and organs homogenates. Moreover, malonidialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) as well as lipid profile were also measured. Results showed that exposure to rifampicin and CCl4 respectively caused a marked derangement in lipid profile as well as decrease in SOD and CAT activity relative to the negative control. Administration of both toxicants also caused a marked increase in serum ALT, AST, ALP, urea, uric acid and creatine kinase compared to the negative control. Treatment with P. amarus attenuated the toxicity imposed by rifampicin and CCl4 on the liver and kidney in a dose-dependent fashion. All biochemical indices measured were restored to values comparable with animals treated with silymarin. Histopathological results of the hepatic and renal tissues from the various groups of experimental animals gave credence to the curative effects of P. amarus leaf extract on damaged liver and kidney cells. Put together, P. amarus is a potential medicinal plant with similar potency to conventional drugs currently in use for the treatment liver and kidney diseases. Hence, it is a viable therapeutic alternative that can be exploited for the treatment of renal and hepatic diseases.
Broiler chickens are highly sensitive to high ambient temperatures due to their feathers, lack of skin sweat glands, and high productivity. Heat stress (HS) is a major concern for the poultry industry because it negatively affects growth as well as immune functions, which increase the potential risk of infectious disease outbreaks. Therefore, it is vital to elucidate HS's effect on the avian immune system, especially considering the global rise in average surface temperature. Our study identified a series of immunological disorders in heat-stressed broiler chickens. We exposed 22-day-old broiler chickens to a continuous HS condition (34.5 ± 0.5°C) for 14 days and immunized them with a prototype bovine serum albumin (BSA) antigen. The plasma and lymphoid tissues (thymus, bursa of Fabricius, and spleen) were harvested at the end of the experiments to investigate the induction of BSA-specific immune responses. Our results revealed that plasma titers of immunoglobulin (Ig)Y, IgM, and IgA antibodies specific for BSA were lower than those of thermoneutral chickens immunized with BSA. Furthermore, the spleens of the heat-stressed broiler chickens displayed severe depression of Bu1⁺ B cells and CD3⁺ T cells, including CD4⁺ T cells and CD8⁺ T cells, and lacked a fully developed germinal center (GC), which is crucial for B cell proliferation. These immunological abnormalities might be associated with severe depression of CD4⁻CD8⁻ or CD4⁺CD8⁺ cells, which are precursors of either helper or killer T cells in the thymus and Bu1⁺ B cells in the bursa of Fabricius. Importantly, HS severely damaged the morphology of the thymic cortex and bursal follicles, where functional maturation of T and B cells occur. These results indicate that HS causes multiple immune abnormalities in broiler chickens by impairing the developmental process and functional maturation of T and B cells in both primary and secondary lymphoid tissues.
The peripheral nervous system communicates specifically with the immune system via local interactions. These interactions include the “hardwiring” of sympathetic/parasympathetic (efferent) and sensory nerves (afferent) to primary (e.g., thymus and bone marrow) and secondary (e.g., lymph node, spleen, and gut-associated lymphoid tissue) lymphoid tissue/organs. To gain a better understanding of this bidirectional interaction/crosstalk between the two systems, we have investigated the distribution of nerve fibres and PNS-immune cell associations in situ in the mouse lymph node by using immunofluorescent staining and confocal microscopy/ three-dimensional reconstruction. Our results demonstrate i) the presence of extensive nerve fibres in all compartments (including B cell follicles) in the mouse lymph node; ii) close contacts/associations of nerve fibres with blood vessels (including high endothelial venules) and lymphatic vessels/sinuses; iii) close contacts/associations of nerve fibres with various subsets of dendritic cells (e.g., B220+CD11c+, CD4+CD11c+, CD8a+CD11c+, and Mac1+CD11c+), Mac1+ macrophages, and B/T lymphocytes. Our novel findings concerning the innervation and nerve-immune cell interactions inside the mouse lymph node should greatly facilitate our understanding of the effects that the peripheral nervous system has on cellular- and humoral-mediated immune responses or vice versa in health and disease.
This study aims to investigate the effects of epigallocatechin gallate (EGCG) on the growth performance and serum metabolic characteristics of heat-stressed broilers. A total of 192 14-day-old Arbor Acres broilers were divided into 4 groups with 6 replicates per group (8 chickens/cage). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300, and 600 mg/kg diet (Groups HS0, HS300, and HS600, respectively). The production performance and serum metabolic characteristics were analyzed at d 21, 28, and 35, respectively. At d 35 of age, heat stress reduced (P < 0.05) the body weight (BW), feed intake (FI) and the contents of serum total protein (TP) and glucose (GLU); inhibited (P < 0.05) alkaline phosphatase (ALP) activity; But increased (P < 0.05) the contents of uric acid (UA), cholesterol (CHOL), triglyceride (TG), and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST). Heat-stressed chickens fed EGCG exhibited a linear increase (P < 0.05) in BW, FI, the levels of serum TP, GLU, and ALP activity; and linear decrease (P < 0.05) in the contents of serum UA, CHOL, and TG, as well as the activities of LDH, CK, and AST. Heat stress also reduced (P < 0.05) the activities of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) on d 35 and increased (P < 0.05) the GSH-Px and SOD activity on d 21 and malondialdehyde (MDA) contents. There was a linear increase (P < 0.05) in activities of GSH-Px, SOD and CAT at 35 d of age, and linear decreased (P < 0.05) in MDA contents. In conclusion, EGCG can improve the growth performance of broilers by enhancing antioxidant property and alleviating oxidant damage caused by heat stress.
Exposure of chicks to a high ambient temperature (HT) has previously been shown to increase neuropeptide Y (NPY) mRNA expression in the brain. Furthermore , it was found that NPY has anti-stress functions in heat-exposed fasted chicks. The aim of the study was to reveal the role of central administration of NPY on thermotolerance ability and the induction of heat-shock protein (HSP) and NPY sub-receptors (NPYSRs) in fasted chicks with the contribution of plasma metabolite changes. Six-or seven-day-old chicks were centrally injected with 0 or 375 pmol of NPY and exposed to either HT (35 AE 1°C) or control thermoneutral temperature (CT: 30 AE 1°C) for 60 min while fasted. NPY reduced body temperature under both CT and HT. NPY enhanced the brain mRNA expression of HSP-70 and-90, as well as of NPYSRs-Y5,-Y6, and-Y7, but not-Y1,-Y2, and-Y4, under CT and HT. A coinjection of an NPYSR-Y5 antagonist (CGP71683) and NPY (375 pmol) attenuated the NPY-induced hypothermia. Furthermore, central NPY decreased plasma glucose and triacylglycerol under CT and HT and kept plasma corticosterone and epinephrine lower under HT. NPY increased plasma taurine and anserine concentrations. In conclusion, brain NPYSR-Y5 partially afforded protective thermotolerance in heat-exposed fasted chicks. The NPY-mediated reduction in plasma glucose and stress hormone levels and the increase in free amino acids in plasma further suggest that NPY might potentially play a role in minimizing heat stress in fasted chicks.
The liver plays a central role in metabolism and is important in maintaining homeostasis throughout the body. This study integrated transcriptomic and metabolomic data to understand how the liver responds under chronic heat stress. Chickens from a rapidly growing broiler line were heat stressed for 8 hours per day for one week and liver samples were collected at 28 days post hatch. Transcriptome analysis reveals changes in genes responsible for cell cycle regulation, DNA replication, and DNA repair along with immune function. Integrating the metabolome and transcriptome data highlighted multiple pathways affected by heat stress including glucose, amino acid, and lipid metabolism along with glutathione production and beta-oxidation.
Studies bridging neuroscience and immunology have identified neural pathways that regulate immunity and inflammation. Recent research using methodological advances in molecular genetics has improved our understanding of the neural control of immunity. Here we outline mechanistic insights, focusing on translational relevance and conceptual developments. We also summarize findings from recent clinical studies of bioelectronic neuromodulation in inflammatory and autoimmune diseases.
Background
High ambient temperatures cause stress in poultry, especially for broiler lines, which are genetically selected for rapid muscle growth. RNA-seq technology provides powerful insights into environmental response from a highly metabolic tissue, the liver. We investigated the effects of acute (3 h, 35 °C) and chronic (7d of 35 °C for 7 h/d) heat stress on the liver transcriptome of 3-week-old chicks of a heat-susceptible broiler line, a heat-resistant Fayoumi line, and their advanced intercross line (AIL). ResultsTranscriptome sequencing of 48 male chickens using Illumina HiSeq 2500 technology yielded an average of 33.9 million, 100 base-pair, single-end reads per sample. There were 8 times more differentially expressed genes (DEGs) (FDR < 0.05) in broilers (n = 627) than Fayoumis (n = 78) when comparing the acute-heat samples to the control (25 °C) samples. Contrasting genetic lines under similar heat treatments, the highest number of DEGs appeared between Fayoumi and broiler lines. Principal component analysis of gene expression and analysis of the number of DEGs suggested that the AIL had a transcriptomic response more similar to the Fayoumi than the broiler line during acute heat stress. The number of DEGs also suggested that acute heat stress had greater impact on the broiler liver transcriptome than chronic heat stress. The angiopoietin-like 4 (ANGPTL4) gene was identified as differentially expressed among all 6 contrasts. Ingenuity Pathway Analysis (IPA) created a novel network that combines the heat shock protein family with immune response genes. Conclusions
This study extends our understanding of the liver transcriptome response to different heat exposure treatments in distinct genetic chicken lines and provides information necessary for breeding birds to be more resilient to the negative impacts of heat. The data strongly suggest ANGPTL4 as a candidate gene for improvement of heat tolerance in chickens.
Heat stress (HS) negatively affects human health, animal welfare, and livestock production. We analyzed the hepatic proteomes of finishing pigs subjected to chronic heat stress (HS), thermal neutral (TN), and restricted feed intake conditions, identifying differences between direct and indirect (via reduced feed intake) HS. Twenty-four castrated male pigs were randomly allocated to three treatments for three weeks: (1) thermal neutral (TN) (22 °C) with ad libitum feeding; (2) chronic HS (30 °C) with ad libitum feeding; and (3) TN, pair-fed to HS intake (PF). Hepatic proteome analysis was conducted using two-dimensional gel electrophoresis and mass spectrometry. Both HS and PF significantly reduced liver weight (p < 0.05). Forty-five hepatic proteins were differentially abundant when comparing HS with TN (37), PF with TN (29), and HS with PF (16). These proteins are involved in heat shock response and immune defense, oxidative stress response, cellular apoptosis, metabolism, signal transduction, and cytoskeleton. We also observed increased abundance of proteins and enzymes associated with heat shock response and immune defense, reduced the redox state, enhanced multiple antioxidant abilities, and increased apoptosis in HS liver. Heat-load, independent of reduced feed intake, induced an innate immune response, while food restriction caused stress and cellular apoptosis. Our results provide novel insights into the effects of chronic HS on liver.
One-day old chicks were randomly distributed into acute heat stress (AHS) or persistent heat stress (PHS) groups. Each group was further divided into control (CK), and three AHS ages (1, 2, or 3 weeks of age) experimental subgroups. The chicks in AHS subgroups were submitted to acute heat stress (40 degrees C for two hours between 12: 00 and 14: 00 hours during the weekend) and the effects of heat stress on several daily behaviors were observed. At 8 days of age, the chicks of PHS subgroups were submitted to heat stress (40 degrees C daily). The heat treatment ceased during the weekends and the effects on the behavior were observed three times daily for three consecutive days. The results showed that, compared with the CK group, the duration and frequency of drinking and lying-down behaviors of the AHS birds increased, whereas the duration of feeding and standing significantly decreased (p<0.01). The time spent walking by PHS birds was significantly longer than that of the CK groups (p<0.01), and drinking was also significantly longer than that of the CK group and was significantly different when birds were three weeks old (p=0.05). When heat stress lasted for two and three weeks in PHS group, the duration of lying down was longer compared with the CK group; however, this behavior was significantly shorter than the CK group when birds were three weeks old (p<0.05). These results indicate that heat stress significantly affects the daily behavior of broilers, including feeding, drinking, lying, standing, and walking.
The objective of this study was to explore the linkage of oxidative stress occurring in mitochondria, skeletal muscles, and plasma in heat stress-challenged broilers. At d 35, 24 broilers were randomly assigned to 2 treatments: rearing at high temperature (32 ± 1°C; heat stress group) or normal temperature (21 ± 1.2°C; control) for 7 d. The oxidative damage of lipid, DNA, and protein and the activities of antioxidative enzymes were measured, respectively, in plasma, skeletal muscles (breast and thigh muscles), and skeletal muscle mitochondria. The result showed that heat exposure increased ( < 0.01) plasma concentrations of thiobarbituric acid reacting substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) whereas it deceased total antioxidant capacity ( < 0.05) and ability to inhibit hydroxyl radicals (AIHR; < 0.001). Protein carbonyl and TBARS levels were increased ( < 0.001) by heat stress in breast and thigh muscles. In skeletal muscle mitochondria, heat stress increased ( < 0.05) 8-OHdG and suppressed AIHR. Plasma activity of superoxide dismutase (SOD) was increased ( < 0.001) whereas glutathione peroxidase (GSH-Px) was suppressed by heat stress ( < 0.001). Heat exposure increased SOD and catalase activities in breast muscle ( < 0.01) but the reverse was true in thigh muscle ( < 0.05). Glutathione peroxidase was increased in thigh muscle ( < 0.001) but was not changed in breast muscle ( > 0.05). Heat stress increased SOD ( < 0.05) and decreased GSH-Px activities ( < 0.05) of mitochondria regardless of muscle types. Plasma allantoin level increased ( < 0.01) correspondingly with urate ( < 0.001) in heat-stressed broilers, indicating that urate could serve as an antioxidant to enhance the antioxidative capacity during stress in a concentration-dependent manner. The activities of respiratory chain complexes I and III were estimated in skeletal muscle mitochondria. Mitochondrial complex I activity was suppressed ( < 0.01) by heat exposure in breast and thigh muscles but complex III activity was elevated only in breast muscle ( < 0.01) of heat-stressed broiler. The fatty acid composition in skeletal muscle was not influenced by heat stress. In conclusion, suppressed mitochondrial complex I activity is associated with oxidative stress induced by heat exposure, which, in turn, is linked with the oxidative damages in muscle tissues and plasma.
The survival and viability of sea turtle embryos is dependent upon favourable nest temperatures throughout the incubation period. Consequently, future generations of sea turtles may be at risk from increasing nest temperatures due to climate change, but little is known about how embryos respond to heat stress. Heat shock genes are likely to be important in this process because they code for proteins that prevent cellular damage in response to environmental stressors. This study provides the first evidence of an expression response in the heat shock genes of embryos of loggerhead sea turtles (Caretta caretta) exposed to realistic and near-lethal temperatures (34 °C and 36 °C) for 1 or 3 hours. We investigated changes in Heat shock protein 60 (Hsp60), Hsp70, and Hsp90 mRNA in heart (n=24) and brain tissue (n=29) in response to heat stress. Under the most extreme treatment (36 °C, 3 h), Hsp70 increased mRNA expression by a factor of 38.8 in heart tissue and 15.7 in brain tissue, while Hsp90 mRNA expression increased by a factor of 98.3 in heart tissue and 14.7 in brain tissue. Hence, both Hsp70 and Hsp90 are useful biomarkers for assessing heat stress in the late-stage embryos of sea turtles. The method we developed can be used as a platform for future studies on variation in the thermotolerance response from the clutch to population scale, and can help us anticipate the resilience of reptile embryos to extreme heating events.
Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and composition are mediated by distinct NPY receptor subtypes.
NPY and its analogues, peptide YY (PYY), [Leu31, Pro34]NPY and NPY1336, were infused in incremental doses of 0.3, 1 and 3 μg kg−1 min−1 for 45 min each and the results compared to those obtained in vehicle-infused rats. Renal blood flow was monitored in 15 min intervals, while urine excretion and composition were determined in 15 min collection periods. Plasma renin activity and aldosterone concentrations were measured at the end of the final infusion period.
Relative to vehicle NPY, PYY and [Leu31, Pro34]NPY dose-dependently reduced renal blood flow and increased diuresis, natriuresis and calciuresis with roughly similar potency; NPY1336 slightly but significantly increased renal blood flow but had no effect on diuresis, natriuresis and calciuresis. None of the peptides significantly affected endogenous creatinine clearance or kaliuresis.
Plasma renin activity was significantly reduced by PYY. Quantitatively similar reductions were observed with NPY and [Leu31, Pro34]NPY but failed to reach statistical significance with the given number of experiments. NPY1336 did not reduce plasma renin activity. None of the peptides significantly affected plasma aldosterone concentrations.
In another series of experiments infusion of PYY336 (2 μg kg−1 min−1 for 120 min) did not reduce renal blood flow but significantly enhancd diuresis and natriuresis to a similar extent as the NPY 2 μg kg−1 min−1.
In a final series of experiments the Y1-selective antagonist, BIBP 3226 (1 or 10 μg kg−1 min−1) dose-dependently antagonized reductions of renal blood flow elicited by bolus injections of NPY (0.130 μg kg−1). BIBP 3226 (10 μg kg−1 min−1) also inhibited the effects of a 120 min infusion of NPY (2 μg kg−1 min−1) on renal blood flow but had only minor inhibitory effects on enhancements of diuresis and did not significantly affect enhancements of natriuresis.
We conclude that NPY reduces renal blood via a classical Y1 subtype of NPY receptor. In contrast enhancements of diuresis, natriuresis and calciuresis occur via a distinct subtype which resembles the receptor that mediates NPY-induced enhancement of food intake.
British Journal of Pharmacology (1997) 120, 1335–1343; doi:10.1038/sj.bjp.0701028
Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit,
the inflammatory reflex, inhibits tumor necrosis factor–α production in spleen by a mechanism requiring acetylcholine signaling
through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the
enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic
signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory
reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation.
Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine,
required to control innate immune responses.
The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects.
It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry.
GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls.
This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.
Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. The aim of this study was to determine if mood disorders and SCZ are associated with abnormal GSH and its functionally related enzymes. Post-mortem prefrontal cortex from patients with BD, MDD, SCZ, and from non-psychiatric comparison controls were provided by the Stanley Foundation Neuropathology Consortium. Spectrophotometric analysis was utilized for the quantitative determination of GSH, while immunoblotting analyses were used to examine expression of glutamyl-cysteine ligase (GCL), GSH reductase (GR), and GSH peroxidase (GPx). We found that the levels of reduced, oxidized, and total GSH were significantly decreased in all psychiatric conditions compared to the control group. Although GCL and GR levels did not differ between groups, the levels of GPx were reduced in MDD and SCZ compared to control subjects. Since oxidative damage has been demonstrated in MDD, BD, and SCZ, our finding that GSH levels are reduced in post-mortem prefrontal cortex suggests that these patient groups may be more susceptible to oxidative stress.
Xanthine oxidase is a molybdenum-containing enzyme catalyzing the hydroxylation of a sp(2)-hybridized carbon in a broad range of aromatic heterocycles and aldehydes. Crystal structures of the bovine enzyme in complex with the physiological substrate hypoxanthine at 1.8 A resolution and the chemotherapeutic agent 6-mercaptopurine at 2.6 A resolution have been determined, showing in each case two alternate orientations of substrate in the two active sites of the crystallographic asymmetric unit. One orientation is such that it is expected to yield hydroxylation at C-2 of substrate, yielding xanthine. The other suggests hydroxylation at C-8 to give 6,8-dihydroxypurine, a putative product not previously thought to be generated by the enzyme. Kinetic experiments demonstrate that >98% of hypoxanthine is hydroxylated at C-2 rather than C-8, indicating that the second crystallographically observed orientation is significantly less catalytically effective than the former. Theoretical calculations suggest that enzyme selectivity for the C-2 over C-8 of hypoxanthine is largely due to differences in the intrinsic reactivity of the two sites. For the orientation of hypoxanthine with C-2 proximal to the molybdenum center, the disposition of substrate in the active site is such that Arg(880) and Glu(802), previous shown to be catalytically important for the conversion of xanthine to uric acid, play similar roles in hydroxylation at C-2 as at C-8. Contrary to the literature, we find that 6,8-dihydroxypurine is effectively converted to uric acid by xanthine oxidase.
This study investigated the effects of different acute high ambient temperatures on dysfunction of hepatic mitochondrial respiration, the antioxidative enzyme system, and oxidative injury in broiler chickens. One hundred twenty-eight 6-wk-old broiler chickens were assigned randomly to 4 groups and subsequently exposed to 25 (control), 32, 35, and 38 degrees C (RH, 70 +/- 5%) for 3 h, respectively. The rectal temperatures, activity of antioxidative enzymes (superoxide dismutase, catalase, and glutathione peroxidase), content of malondialdehyde and protein carbonyl, and the activity of mitochondrial respiratory enzymes were determined. The results showed that exposure to high ambient temperature induced a significant elevation of rectal temperature, antioxidative enzyme activity, and formation of malondialdehyde and protein carbonyl, as well as dysfunction of the mitochondrial respiratory chain in comparison with control (P < 0.05). Almost all of the indicators changed in a temperature-dependent manner with the gradual increase of ambient temperature from 32 to 38 degrees C; differences in each parameter (except catalase) among the groups exposed to different high ambient temperatures were also statistically significant (P < 0.05). The results of the present study suggest that, in the broiler chicken model used here, acute exposure to high temperatures may depress the activity of the mitochondrial respiratory chain. This inactivation results subsequently in overproduction of reactive oxygen species, which ultimately results in oxidative injury. However, this hypothesis needs to be evaluated more rigorously in future studies. It has also been shown that, with the gradual increase in temperature, the oxidative injury induced by heat stress in broiler chickens becomes increasingly severe, and this stress response presents in a temperature-dependent manner in the temperature range of 32 to 38 degrees C.
The aim of this study was to examine the central action of taurine on body temperature and food intake in neonatal chicks under control thermoneutral temperature (CT) and high ambient temperature (HT). Intracerebroventricular injection of taurine caused dose-dependent hypothermia and reduced food intake under CT. The mRNA expression of the GABAA receptors, GABAAR-α1 and GABAAR-γ, but not that of GABABR, significantly decreased in the diencephalon after central injection of taurine. Subsequently, we found that picrotoxin, a GABAAR antagonist, attenuated taurine-induced hypothermia. Central taurine significantly decreased the brain concentrations of 3-methoxy-4-hydroxyphenylglycol, a major metabolite of norepinephrine; however, the concentrations of serotonin, dopamine, and the epinephrine metabolites, 3,4-hydroxyindoleacetic acid and homovanillic acid, were unchanged. Although hypothermia was not observed under HT after central injection of taurine, plasma glucose and uric acid levels were higher, and plasma sodium and calcium levels were lower, than those in chicks under CT. In conclusion, brain taurine may play a role in regulating body temperature and food intake in chicks through GABAAR. The changes in plasma metabolites under heat stress suggest that brain taurine may play an important role in maintaining homeostasis in chicks.
Oral administration of sucralose has been reported to stimulate food intake through inducing hypothalamic neuropeptide Y (NPY) in mice and fruit flies. However, the underlying mechanisms of action of sucralose in hypothermia and NPY and monoamine regulation remain unknown. The aim of the present study was to investigate central effects of sucralose on body temperature, NPY, and monoamine regulation, as well as its peripheral effects, in chicks. In Experiment 1, 5-day-old chicks were centrally injected with 1 μmol of sucralose, other sweeteners (erythritol and glucose), or saline. In Experiment 2, chicks were centrally injected with 0.2, 0.4, and 1.6 μmol of sucralose or saline. In Experiment 3, chicks were centrally injected with 0.8 μmol of sucralose or saline, with a co-injection of 100 μg fusaric acid (FA), an inhibitor of dopamine-β-hydroxylase, to examine the role dopamine in sucralose induced hypothermia. In Experiment 4, 7–16-day-old chicks were orally administered with 75, 150, and 300 mg/2 ml distilled water or sucralose, daily. We observed that the central injection of sucralose, but not other sweeteners, decreased body temperature (P < .05) in chicks; however, the oral injection did not influence body temperature, food intake, and body weight gain. Central sucralose administration decreased dopamine and serotonin and stimulated dopamine turnover rate in the hypothalamus significantly (P < .05). Notably, sucralose co-injection with FA impeded sucralose-induced hypothermia. Sucralose decreases body temperature potentially via central monoaminergic pathways in the hypothalamus.
This study was conducted to investigate the effects of dietary GABA supplementation on blood biochemical parameters, the overall growth performance, and the relative mRNA expression of some FI- regulating genes in broiler chickens. A total of 192, three-day old chicks of mixed sex from two commercial broiler strains (Ross 308 and Cobb 500) were distributed into 2 groups; a control group and GABA-supplemented group (100 mg/kg diet). When the chicks reached 21 days of age, each group of each strain was randomly subdivided into two subgroups: one was exposed to HS (33 ± 2 °C for 5 h/day for 2 weeks), while the other remained at thermoneutral temperature (24 °C). GABA significantly improved bird growth performance under normal and HS conditions, by increasing body weight (BW), weight gain (WG), and FI and significantly reduced the elevated body temperature of birds under HS. GABA supplementation increased FI by reducing the mRNA expression levels of FI-inhibiting neuropeptides, such as POMC, leptin, Ghrelin, and CCK, during HS and by increasing the expression of FI-stimulating neuropeptides such as AgRP and NPY. Moreover, GABA significantly altered FAS and ACC gene expression, resulting in significant increases in abdominal fat content in birds reared normally. In contrast, GABA lowered fat content in Cobb birds and increased it in Ross birds under HS. Therefore, GABA (100 mg/kg diet) is a strong FI-stimulating neurotransmitter and its regulatory effects depend on broiler strain and housing temperature.
Exposure to continuous life stress often causes gastrointestinal (GI) symptoms. Studies have shown that neuropeptide Y (NPY) counteracts the biological actions of corticotrophin-releasing factor (CRF), and is involved in the termination of the stress response. However, in chronic repeated restraint stress (CRS) conditions, the actions of NPY on GI motility remain controversial. To evaluate the role of NPY in mediation of the adaptation mechanism and GI motility in CRS conditions, a CRS rat model was set up. Central CRF and NPY expression levels were analyzed, serum corticosterone and NPY concentrations were measured, and GI motor function was evaluated. The NPY Y1 receptor antagonist BIBP-3226 was centrally administered before stress loading, and on days, 1-5, of repeated stress, the central CRF and the serum corticosterone concentrations were measured. In addition, gastric and colonic motor functions were evaluated. The elevated central CRF expression and corticosterone concentration caused by acute stress began to fall after 3 days of stress loading, while central NPY expression and serum NPY began to increase. GI dysmotility also returned to a normal level. Pretreatment with BIBP-3226 abolished the adaptation mechanism, and significantly increased CRF expression and the corticosterone concentration, which resulted in delayed gastric emptying and accelerated fecal pellet output. Inhibited gastric motility and enhanced distal colonic motility were also recorded. CRS-produced adaptation, over-expressed central CRF, and GI dysmotility observed in acute restraint stress were restored to normal levels. Central NPY via the Y1 receptor plays an important role in mediating the adaptation mechanism against chronic stress.
Recently, we demonstrated that brain neuropeptide Y (NPY) mRNA expression was increased in heat exposed chicks. However, the functions of brain NPY during heat stress are unknown. This study was conducted to investigate whether centrally administered NPY affects food intake, rectal temperature, monoamines, stress hormones and plasma metabolites in chicks under high ambient temperatures (HT). Five or six-day-old chicks were centrally injected with 0, 188 or 375 pmol of NPY and exposed to either HT (35 ± 1 °C) or a control thermoneutral temperature (CT; 30 ± 1 °C) for 3 h whilst fed or fasted. NPY increased food intake under both CT and HT. NPY reduced rectal temperature 1 and 2 h after central administration under CT, but not under HT. Interestingly, NPY decreased brain serotonin and norepinephrine concentrations in fed chicks, but increased concentrations of brain dopamine and its metabolites in fasted and fed chicks, respectively. Plasma epinephrine was decreased by NPY in fed chicks, but plasma concentrations of norepinephrine and epinephrine were increased significantly by NPY in fasted-heat exposed chicks. Furthermore, NPY significantly reduced plasma corticosterone concentrations in fasted chicks. Plasma glucose and triacylglycerol were increased by NPY in fed chicks, but triacylglycerol declined in fasted NPY-injected chicks. In conclusion, brain NPY may attenuate the reduction of food intake during heat stress and the increased brain NPY might be a potential regulator of the monoamines and corticosterone to modulate stress response in heat-exposed chicks.
... Thomas D Schmittgen 1 & Kenneth J Livak 2 . ABSTRACT. ... N. Engl. J . Med. ... 32, e178 (2004). | Article | PubMed | ChemPort |; Livak , KJ & Schmittgen , TD Analysis of relative gene expression data using real - time quantitative PCR and the 2 (- Delta Delta C(T)) Method . ...
... Thomas D Schmittgen 1 & Kenneth J Livak 2 . ABSTRACT. ... N. Engl. J . Med. ... 32, e178 (2004). | Article | PubMed | ChemPort |; Livak , KJ & Schmittgen , TD Analysis of relative gene expression data using real - time quantitative PCR and the 2 (- Delta Delta C(T)) Method . ...
The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes.
The dry chemistry system was applied to the blood chemical examination of chickens. The values obtained from 13-week-old “Takachiho” chickens (5 males, 5 females) and 8-week-old broilers (12 males, 9 females) were evaluated. The following laboratory parameters were included: total protein (TP), albumin (Alb), potassium (K), uric acid (UA), blood urea nitrogen (BUN), total bilirubin (T-Bil), glucose (Glu), triglycerides (TG), total cholesterol (T-CHO), transaminase (GOT, GPT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), γ-glutamyl transpeptidase (γ-GTP), creatine phosphokinase (CPK) and amylase (Amy).
There were little significant differences in the serum biochemical profile between the 2 breeds of chickens. Chickens had lower values for TP and higher Glu levels than those of mammals. UA values were extremely high and BUN levels were lower than 3.Omg/dl. Serum enzymes, except for GPT and γ-GTP, revealed obvious high activities and wide variations. Most of the reference values obtaind by the dry chemistry system compared favorably with the published data by the use of conventional methods. From these results, it was conclude that the dry chemistry system may be useful for blood chemical analysis in chickens. It is necessary to collect more data for each laboratory parameter so as to establish the normal range, thereby evaluating properly the values measured with chickens.
Acute heat stress severely impacts poultry production. The hypothalamus acts as a crucial center to regulate body temperature, detect temperature changes, and modulate the autonomic nervous system and endocrine loop for heat retention and dissipation. The purpose of this study was to investigate global gene expression in the hypothalamus of broiler-type B strain Taiwan country chickens after acute heat stress. Twelve 30-week-old hens were allocated to four groups. Three heat-stressed groups were subjected to acute heat stress at 38 °C for 2 hours without recovery (H2R0), with 2 hours of recovery (H2R2), and with 6 hours of recovery (H2R6). The control hens were maintained at 25 °C. At the end, hypothalamus samples were collected for gene expression analysis. The results showed that 24, 11, and 25 genes were upregulated and 41, 15, and 42 genes were downregulated in H2R0, H2R2, and H2R6 treatments, respectively. The expressions of gonadotropin-releasing hormone 1 (GNRH1), heat shock 27-kDa protein 1 (HSPB1), neuropeptide Y (NPY), and heat shock protein 25 (HSP25) were upregulated at all recovery times after heat exposure. Conversely, the expression of TPH2 was downregulated at all recovery times. A gene ontology analysis showed that most of the differentially expressed genes were involved in biological processes including cellular processes, metabolic processes, localization, multicellular organismal processes, developmental processes, and biological regulation. A functional annotation analysis showed that the differentially expressed genes were related to the gene networks of responses to stress and reproductive functions. These differentially expressed genes might be essential and unique key factors in the heat stress response of the hypothalamus in chickens.
Heat stress has negative effects on biological defense mechanisms such as the immune response in chickens, and organs of the immune system, such as the spleen, are atrophied by heat stress in broiler chickens. In order to assess heat stress-induced functional changes of immune mechanisms in the spleen of broiler chickens, expression of genes encoding splenic cytokines (Th1 type, Th2 type, and pro-inflammatory cytokines) was analyzed. Heat exposure at 34°C for 15 days significantly induced the spleen involution, increased interleukin (IL)-4 and IL-12 expression and decreased interferon (IFN)-γ. However, expression of IL-6, 10, 13, and 18 was not affected. Heat stress reduced feed intake, which may affect the spleen weight and cytokine expression. Therefore, a pair-fed group at 24? (24PF) was included in which chickens received the same amount of feed as those in the group at 34°C. Spleen weight was not affected by the reduction in feed intake. IL-4 expression in the 24PF group was higher than that in the control group. Further, IFN-γ expression increased and IL-12 expression was not affected by the reduction of feed intake, suggesting that the feed intake reduction induced by heat stress does not modulate splenic cytokine expression in broiler chickens. These data suggest that heat stress induces spleen involution and affects the expression of splenic cytokines such as IL-12 and IFN-γ in broiler chickens, but not through the feed intake reduction.
Some amino acids are important regulators of key metabolic pathways and therefore necessary for several physiological functions. However, little is know about thermoregulatory functions of amino acids. In this study, therefore chicks were either centrally or orally administered with L-citrulline (L-Cit), L-arginine (L-Arg) or L-ornithine (L-Orn) to monitor changes in rectal temperature. In Experiment 1, the amino acids (L-Cit, L-Arg and L-Orn) were administered into the left ventricle of the chicks by intracerebroventicular (i.c.v.) injection at a dose of 1 μmol/10 μl to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period. In Experiment 2, chicks received the same amino acids by oral administration at a dose of 15 mmol/10 ml/kg body weight. In Experiment 3, chicks received three doses of L-Cit (3.75, 7.5 or 15 mmol/10 ml/kg body weight) by oral administration. I.c.v. injection with any of the amino acids studied did not alter body temperature, but oral administration of L-Cit significantly reduced body temperature. Importantly, the highest does effectively reduced body temperature. These results suggest that peripheral L-Cit has a hypothermic function in chicks, which may be a new candidate to minimize high body temperature in poultry during summer heat stress.
Within the neuropeptide Y (NPY) family of peptides, pancreatic polypeptide is the most divergent across species. It differs in 20 of 36 positions between human and chicken. In mammals, it binds primarily to the Y4 receptor, to which NPY and peptide YY (PYY) bind with lower affinities. Because of these large sequence differences in pancreatic polypeptide, we decided to characterise the chicken Y4 receptor. We report here that Y4 displays the least sequence conservation among the Y-family receptors, with only 57-60% overall amino acid identity between chicken and mammals, compared with 64-83% for the Y1, Y2 and Y5 receptors. After expression of the chicken Y4 receptor in COS-7 cells, (125)I-labelled porcine (p) PYY bound with a K(d) of 20 pM. In competition with (125)I-pPYY, chicken pancreatic polypeptide bound with high affinity at 140 pM. Interestingly, chicken PYY bound with even greater affinity at 68 pM. The affinity of NPY, 160 pM, was similar to that of pancreatic polypeptide. Chicken Y4 is less sensitive than is mammalian Y4 to truncation of the amino terminus of the NPY molecule. RT-PCR revealed expression in several peripheral organs, including adipose tissue and oviduct. In brain, Y4 mRNA was detected in the brainstem, cerebellum and hippocampus. In situ hybridisation to brain sections showed expression in the dorsal motor nucleus of the vagus in the brainstem. Thus the chicken Y4 receptor is less selective and anatomically more widespread than that in mammals, probably reflecting the original properties of the Y4 receptor.
Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1°C for 2 or 5h) or to a control thermoneutral temperature (CT; 30±1°C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake.
Copyright © 2015. Published by Elsevier Inc.
The effects of taurine supplementation on growth performance, serum and liver concentrations of lipid, fatty acid composition and lipid peroxidation in the livers of broilers under chronic heat exposure conditions were investigated. The chicks with a similar body weight were equally assigned to one of three controlled-environment chambers. The brolier chicks, which were kept at 34°C were fed either with a control diet or the control diet supplemented with 0.8% taurine, whereas broiler chicks kept at 22°C were fed a control diet. Both of the BW and BW gains of broilers maintained at a temperature of 34°C were significantly lower than those of the control group, which was maintained at a temperature of 22°C (p<0.05). However, taurine addition in the diet of birds submitted to heat stress siginficantly improved BW gain (p<0.05). The feed intake of chicks declined with increases in temperature. The relative liver and gall bladder weights of chicks fed the control diet and maintained at 34°C were significantly lower than those measured in the control birds (p<0.05). However, dietary taurine was found to compensate for these reductions in liver and gall bladder weights. Relative weights of abdominal fat did not differ significantly among the three groups. Serum triglyceride concentrations were significantly lower in the chicks fed the control diet and maintained at 34°C compare to those measured in the chicks fed the control diet at 22°C (p<0.05). Heat stress resulted in a significant reduction in total lipid and triglyceride levels, but also increased the levels of total cholesterol in the liver (p<0.05). However, dietary taurine supplementation under the heat stress condition resulted in the recovery, to control levels, of serum triglyceride concentrations, as well as the amounts of total lipids, triglycerides, and cholesterol in the liver. The livers of chicks fed on taurine diets at 34°C showed significantly higher proportions of C14:0, C16:1, C18:1, C18:2, and 20:3. and lower C18:0 and C20:4 proportions than those of chicks fed on control diets at the same temperature (p<0.05). The total levels of saturated fatty acids decreased, but monounsaturated fatty acids and unsaturated fatty acid levels increased in chicks fed the taurine diet, as compared to chicks fed the control diet at 34°C (p<0.05). Peroxidizability indices were significantly lower in the heat-exposed chicks fed the taurine diet than in the non-taurine heat-exposed groups (p<0.05). In conclusion, dietary taurine results in an increase in the growth performances of chicks under heat stress conditions via improvements in lipid absorption and metabolism, as well as an induced reduction in lipid peroxidation.
Aims:
L-Aspartate (L-Asp) and D-aspartate (D-Asp) are physiologically important amino acids in mammals and birds. However, the functions of these amino acids have not yet been fully understood. In this study, we therefore examined the effects of L-Asp and D-Asp in terms of regulating body temperature, plasma metabolites and catecholamines in chicks.
Main methods:
Chicks were first orally administered with different doses (0, 3.75, 7.5 and 15 mmol/kg body weight) of L- or D-Asp to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period.
Key findings:
Oral administration of D-Asp, but not of L-Asp, linearly decreased the rectal temperature in chicks. Importantly, orally administered D-Asp led to a significant reduction in body temperature in chicks even under high ambient temperature (HT) conditions. However, centrally administered D-Asp did not significantly influence the body temperature in chicks. As for plasma metabolites and catecholamines, orally administered D-Asp led to decreased triacylglycerol and uric acid concentrations and increased glucose and chlorine concentrations but did not alter plasma catecholamines.
Significance:
These results suggest that oral administration of D-Asp may play a potent role in reducing body temperature under both normal and HT conditions. The alteration of plasma metabolites further indicates that D-Asp may contribute to the regulation of metabolic activity in chicks.
High ambient temperatures (HT) reduce food intake and body weight in young chickens, and HT can cause increased expression of hypothalamic neuropeptides. The mechanisms by which HT act, and the effects of HT on cellular homeostasis in the brain, are however not well understood. In the current study lipid peroxidation and amino acid metabolism were measured in the brains of 14 d old chicks exposed to HT (35 °C for 24 or 48 h) or to control thermoneutral temperature (CT; 30 °C). Malondialdehyde (MDA) was measured in the brain to determine the degree of oxidative damage. HT increased body temperature and reduced food intake and body weight gain. HT also increased diencephalic oxidative damage after 48 h, and altered some free amino acid concentrations in the diencephalon. Diencephalic MDA concentrations were increased by HT and time, with the effect of HT more prominent with increasing time. HT altered cystathionine, serine, tyrosine and isoleucine concentrations. Cystathionine was lower in HT birds compared with CT birds at 24 h, whilst serine, tyrosine and isoleucine were higher at 48 h in HT birds. An increase in oxidative damage and alterations in amino acid concentrations in the diencephalon may contribute to the physiological, behavioral and thermoregulatory responses of heat-exposed chicks.
Neuropeptide Y (NPY) has been implicated in the modulation of important features of neuronal physiology, including calcium homeostasis, neurotransmitter release and excitability. Moreover, NPY has been involved as an important modulator of hippocampal and thalamic circuits, receiving particular attention as an endogenous antiepileptic peptide and as a potential master regulator of feeding behavior. NPY not only inhibits excessive glutamate release (decreasing circuitry hyperexcitability) but also protects neurons from excitotoxic cell death. Furthermore, NPY has been involved in the modulation of the dynamics of dentate gyrus and subventricular zone neural stem cell niches. In both regions, NPY is part of the chemical resource of the neurogenic niche and acts through NPY Y1 receptors to promote neuronal differentiation. Interestingly, NPY is also considered a neuroimmune messenger. In this review, we highlight recent evidences concerning paracrine/autocrine actions of NPY involved in neuroprotection, neurogenesis and neuroinflammation. In summary, the three faces of NPY, discussed in the present review, may contribute to better understand the dynamics and cell fate decision in the brain parenchyma and in restricted areas of neurogenic niches, in health and disease.
Broiler chicks eat more food than layer chicks. However, the causes of the difference in food intake in the neonatal period between these strains are not clear. In this study, we examined the involvement of proopiomelanocortin (POMC)-derived melanocortin peptides α-, β- and γ-melanocyte-stimulating hormones (MSHs) in the difference in food intake between broiler and layer chicks. First, we compared the hypothalamic mRNA levels of POMC between these strains and found that there was no significant difference in these levels between broiler and layer chicks. Next, we examined the effects of central administration of MSHs on food intake in these strains. Central administration of α-MSH significantly suppressed food intake in both strains. Central administration of β-MSH significantly suppressed food intake in layer chicks, but not in broiler chicks, while central administration of γ-MSH did not influence food intake in either strain. It is therefore likely that the absence of the anorexigenic effect of β-MSH might be related to the increased food intake in broiler chicks.
Neuropeptide Y (NPY) is a sympathetic cotransmitter and a platelet-derived factor which causes vasoconstriction, potentiation of norepinephrine (NE) action, and vascular mitogenic effects. Reciprocally, NE markedly enhances the actions of NPY. We studied vasopressor effects of NPY and sources of peptide release during the development of hypertension in spontaneously hypertensive rats (SHR). Conscious SHR (4 and 16 weeks old) had higher resting plasma levels of NE and epinephrine than age-matched Wistar-Kyoto (WKY) rats, but similar NPY immunoreactivity (NPY-ir) levels in platelet-poor plasmas (PPP). In both strains, NPY-ir levels in PPP were higher in 4-week-old than in older rats. However, at all ages (4-24 weeks) SHR had markedly elevated NPY-ir content in platelet-rich-plasmas than WKY rats, although levels declined with age and hypertension. In the superior mesenteric artery, NPY-ir content (per mg) was significantly higher in 4-week-old but lower in 16-week-old SHR than in WKY rats, suggesting greater sympatho-neural NPY stores and release (leading to depletion) during the development of hypertension. Four-week-old SHR also tended to have higher NPY-ir content in the adrenal medullae and coeliac ganglia but a lower content in the kidney than WKY rats; these differences disappeared with age. Pressor responsiveness to alpha-agonists and NPY were similar in both strains at 4 weeks. While unchanged by age in WKY rats, adrenergic and NPY-mediated vasopressor responses became augmented in 16- to 24-week-old SHR (compared with WKY rats); this hyperresponsiveness was not completely abolished by ganglionic blockade and not observed with vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)
The regulation of food intake in chickens (Gallus gallus domesticus) represents a complex homeostatic mechanism involving multiple levels of control, and regulation during high ambient temperatures (HT) is poorly understood. In this study, we examined hypothalamic mRNA expression of gonadotropin-inhibitory hormone (GnIH) to understand the effect of HT on an orexigenic neuropeptide. We examined the effects of HT (35 °C ambient temperature for 1, 24 or 48 h) on 14-day old chicks. HT significantly increased rectal temperature and suppressed food intake, and also influenced plasma metabolites. The expression of GnIH precursor mRNA in the diencephalon was significantly increased in chicks at 24-and 48 h of HT when food intake was suppressed significantly, whilst no change was observed for GnIH precursor mRNA and food intake at 1h of HT. In situ hybridization and immunocytochemistry further revealed the cellular localization of chicken GnIH precursor mRNA and its peptide in the paraventricular nucleus (PVN) in the chick hypothalamus. We examined plasma metabolites in chicks exposed to HT for 1 or 48 h and found that triacylglycerol concentration was significantly higher in HT than control chicks at 1h. Total protein, uric acid and calcium were significantly lower in HT chicks than control chicks at 48h. These results indicate that not only a reduction in food intake and alteration in plasma metabolites but also the PVN-specific expression of GnIH, an orexigenic agent, may be induced by HT. The reduced food intake at the same time as GnIH expression was increased during HT suggests that HT-induced GnIH expression may oppose HT-induced feeding suppression, rather than promote it. We suggest that the increased GnIH expression could be a consequence of the reduced food intake, and would not be a direct response to HT.
Intracerebral injection of C14-labeled L-proline resulted in its distribution in periventricular tissue (including septum, hippocampus, and hypothalamus) in neonatal chicks decapitated 1 min after injection. Delay of decapitation for 3, 9 or 45 min resulted only in an increased spread of label into the fourth ventricle. A simple, effective chick head-holder is also described.
Neuropeptide-Y (NPY) is a 36 amino acid peptide that acts as a chemical messenger in the central and peripheral nervous systems. NPY often is found colocalized with the classical neurotransmitter norepinephrine (NE) and can potentiate the effects of this neurotransmitter postsynaptically in many systems. Using immunocytochemistry for NPY and specific lymphoid cell markers, we mapped the distribution of NPY-positive nerve fibers in the rat spleen. NPY-positive nerve fibers were present along the vasculature, trabeculae, and capsule, and also were found associated with specific lymphoid parenchymal compartments of the spleen, in close contact with lymphocytes and macrophages. These contacts were investigated further at the electron microscopic level. NPY-positive nerve terminals were found in close apposition with lymphocytes in the periarteriolar lymphatic sheath, and with lymphocytes and macrophages in the marginal zone. Previous studies have reported that postganglionic noradrenergic nerve fibers innervate specific lymphoid compartments of the rat spleen, with nerve terminals forming direct appositions with cells of the immune system. The possible colocalization of NPY and NE in these nerve fibers was investigated by chemical sympathectomy with 6-hydroxydopamine, followed by immunocytochemical labeling of NPY and tyrosine hydroxylase (TH), the rate-limiting enzyme in norepinephrine synthesis. Colocalization also was investigated by labeling for NPY with a fluorescent label, eluting the NPY, and staining for TH with diaminobenzidine as the label. These studies demonstrate that norepinephrine and NPY are colocalized in the postganglionic sympathetic nerve fibers of the rat spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
Urate serves as a potent antioxidant by means of radical scavenging and reducing activities. This antioxidant action is partly manifested by interaction with another powerful antioxidant, ascorbic acid, and is particularly evident in species that lack the ability to synthesize ascorbic acid. Urate not only behaves as a radical scavenger but also stabilizes ascorbate in biological fluids. This stabilizing effect appears to be due to an inhibition of iron-catalyzed oxidation of ascorbate. Ascorbate stabilization is particularly evident in human serum and is largely due to iron chelation by urate. Unlike radical-scavenging reactions, this protective effect of urate is not associated with its depletion because a stable, noncatalytic urate-iron complex is formed. Depletion of serum urate results in rapid subsequent oxidation of ascorbate, which is largely iron dependent. Sequential losses of urate and ascorbate significantly reduce the antioxidant capacity of serum.
Norepinephrine (NE)-evoked vasoconstrictor and pressor responses are reduced after prolonged exposure; such desensitization is observed both clinically and experimentally. The vasoconstrictor neuropeptide Y (NPY) coexists with NE in perivascular sympathetic nerves, and the results of both in vivo and in vitro studies have indicated functional cooperation between NE and NPY. We propose that NPY becomes increasingly important in situations of high sympathetic activity associated with blunted NE responses. Prolonged NE infusion in conscious rats resulted in adrenergic desensitization; however, NPY administration restored the responsiveness to NE. In naive rats, NE greatly enhanced the pressor action of NPY. An analogous phenomenon was observed in the rabbit isolated pulmonary artery, which failed to respond to NPY unless preexposed to NE; this action of NE was only partly inhibited by conventional adrenoceptor and Ca2+ influx blockade. Conversely, NPY enhanced NE-evoked constriction, in particular when the alpha-adrenoceptor reserve was eliminated. It is proposed that threshold synergism, in part caused by converging stimulation of phospholipase C, accounts for much of the NPY/NE cooperativity. We conclude that 1) NPY and NE cooperate to produce vasoconstriction, both in vivo and in vitro; 2) NPY has the capacity to reverse adrenergic desensitization but not vice versa; 3) NE enhances NPY-evoked vasoconstriction, in part independently of conventional adrenoceptor blockade; 4) threshold synergism phenomena, but not "receptor-receptor interactions," account for (most of) the observed NPY/NE cooperation; and 5) when present, alpha-adrenoceptor reserve prevents the lowering of the NE threshold by NPY.
It is concluded that several vasoactive peptides are located in splenic nerves. NPY is present in noradrenergic neurones and causes mainly increased vascular resistance. VIP occurs in non-adrenergic neurones of sympathetic origin and induces vasodilation and relaxation of the capsule. Finally, substance P is present in peripheral branches of spinal afferent nerves and causes vasodilation and capsule contraction. Stimulation of the splenic nerves may thus release several vasoactive substances in addition to noradrenaline, exerting a variety of actions.
An experiment was conducted to elucidate the influence of four constant ambient temperatures (20 degrees, 25 degrees, 30 degrees and 35 degrees C) on the performance and physiological reactions of male commercial broiler chicks from 3 to 7 weeks of age. A 12 h light-dark cycle was operated, while relative humidity and air circulation were not controlled. Exposure of broiler chickens to the 20 degrees, 25 degrees, 30 degrees and 35 degrees C treatments showed highly significant (P less than 0.0001) depression in growth rate, food intake and efficiency of food utilization, and a significant increase in water consumption for the 30 degrees and 35 degrees C groups. Mortality was, however, not affected by the temperature treatments. Changes in physiological status, such as increased rectal temperatures, decreased concentration of red blood cells, haemoglobin, haematocrit, and total plasma protein were observed in birds housed in the higher temperature (30 degrees and 35 degrees C) environments. Moreover, in these broiler chickens, there was an increased blood glucose concentration and a decreased thyroid gland weight. These results indicate that continuous exposure of broiler chickens to high ambient temperatures markedly affects their performance and physiological response.
A rich network of NPY-like immunoreactive fibers was found in the paraventricular nucleus and the ventromedial region of the hypothalamus juxtapositioned to the third ventricle, including the median eminence. Brain regions, areas or nuclei found densely innervated by NPY-like immunoreactive fibers included the olfactory bulb region, septal area, organum vasculosum of the lamina terminalis, preoptic periventricular nucleus, hypothalamic periventricular nucleus, medial suprachiasmatic nucleus, subseptal (subfornical) organ, ventromedial hypothalamic nucleus, infundibular nucleus and nucleus tractus solitarius. NPY-like containing perikarya were localized within the hippocampus, bed nucleus of the stria terminalis and surrounding the nucleus rotundus and nucleus of the basal optic root. Since the immunocytochemical study showed that NPY was localized in brain structures known to alter food intake and the compound is a member of the pancreatic polypeptide family, a second study was designed to determine if the neuropeptide altered plasma concentrations of insulin, glucagon and glucose following intracerebroventricular administration. It was found that NPY significantly increased plasma concentration of insulin. It is proposed that two reasons why NPY is such a potent orexigenic agent is that the paraventricular nucleus and structures surrounding the third ventricle throughout the ventromedial hypothalamic region show high levels of NPY-like immunoreactivity. Secondly, NPY effects an increase in plasma insulin in the periphery.
Neuropeptide Y (NPY) is contained in and coreleased with norepinephrine (NE) from sympathetic nerves innervating vascular and cardiac tissues. The effects of NPY infusion on systemic hemodynamics and cardiac performance were compared with those of NE in conscious and pentobarbital sodium-anesthetized rats. A 10-min infusion of NPY (2 nmol.kg-1.min-1) decreased cardiac index (CI) 20% and stroke volume index (SVI) 9% with increases of 20% in mean arterial pressure (MAP) and 48% in total peripheral resistance (TPR). Conversely, NE (1.0 microgram.kg-1.min-1) increased SVI 14%, MAP 29%, and TRP 26%, with no change in CI. Heart rates decreased similarly (approximately 60 beats/min) but only NE-induced bradycardia was reversible by methylatropine nitrate. In anesthetized rats NPY (0.1 nmol.kg-1.min-1) increased left ventricular end-diastolic pressure (LVEDP) 20 +/- 10 mmHg (means +/- SD, n = 7) and decreased dP/dt by 8 +/- 6%. NE (0.07 microgram.kg-1.min-1) produced an equivalent pressor response, however, dP/dt rose 22 +/- 10% whereas LVEDP increased significantly less than with NPY. Thus NPY is a potent vasoconstrictor exerting similar effects to NE on MAP and TPR but, unlike NE, possesses negative inotropic and chronotropic activity.