Central administration of l- and d-aspartate attenuates stress behaviors by social isolation and CRF in neonatal chicks

Intracerebroventricular (i.c.v.) administration of l-aspartate (l-Asp) attenuates stress responses in neonatal chicks, but the mechanism has not been clarified. In the present study, three behavioral experiments were carried out under socially isolated stressful conditions exacerbated by the use of corticotrophin-releasing factor (CRF). In Experiment 1, i.c.v. injection of l-Asp attenuated behavioral stress responses (distress vocalization and active wakefulness) in a dose-dependent manner. Furthermore, l-Asp increased time spent standing/sitting motionless with eyes open and sitting motionless with head dropped (sleeping posture) in comparison with the group receiving CRF alone. In Experiment 2, i.c.v. injection of d-Asp dose-dependently decreased the number of distress vocalizations and the amount of time spent in active wakefulness. d-Asp increased the time spent standing/sitting motionless with eyes open compared with the group receiving CRF alone. In Experiment 3, we directly compared the effect of l-Asp with that of d-Asp. Both l- and d-Asp induced sedative effects under an acutely stressful condition. However, l-Asp, but not d-Asp, increased the time spent in a sleeping posture. These results indicate that both l- and d-Asp, when present in the brain, could induce a sedative effect, while the mechanism for hypnosis in neonatal chicks may be different for l-Asp in comparison with d-Asp.     

Central administration of phosphatidylserine attenuates isolation stress-induced behavior in chicks

The present study investigated whether centrally administered phosphatidylserine (PS) could modify the behavior of chicks under isolation-induced stress. Isolation stress-induced vocalization and spontaneous activity for 10 min, which were attenuated by intracerebroventricular (i.c.v.) injection of PS. The effect of PS was compared with other phospholipids or L-serine, a constituent of PS. Phosphatidylcholine (PC) had no effect on these behavior, but phosphatidylethanolamine (PE) significantly increased vocalizations and spontaneous activity compared with PS. L-Serine similarly decreased isolation-induced vocalizations and spontaneous activity. To clarify the mechanism by which central PS attenuates isolation-induced stress behavior, the contribution of the acetylcholine (ACh) receptor (AChR) was also investigated. PS was co-injected i.c.v. with the muscarinic AChR (M-AChR) antagonist scopolamine or the nicotinic AChR (N-AChR) antagonist hexamethonium. The suppression of vocalizations and spontaneous activity by PS was partially attenuated by scopolamine, but not hexamethonium. These findings indicate that isolation-induced stress behavior are attenuated by PS, acting partially through the M-AChR.     

ICV CRF and isolation stress differentially enhance plasma corticosterone concentrations in layer- and meat-type neonatal chicks

The present study compared the plasma corticosterone concentrations between meat- and layer-type neonatal chicks (Gallus gallus) (1) exposed to isolation-induced stress or (2) injected intracerebroventricularly (ICV) with corticotropin-releasing factor (CRF). Both types of neonatal chicks housed in groups were individually introduced to an open field arena and locomotion and distress-induced vocalizations were monitored for 10 min. The responses of the two strains were remarkably different, with meat-type chicks being less active than layer-type chicks. Distress-induced vocalizations were drastically decreased over time in meat-type chicks while they remained high in layer-type chicks throughout the test. Plasma corticosterone concentrations measured at the end of the test were significantly higher in layer-type chicks than in meat-type ones. Plasma corticosterone concentrations measured 10 min after the ICV injection of CRF were significantly higher in layer- than meat-type chicks. These results indicate that meat-type chicks have either a greater capability to acclimatize to novel environments, or a blunted HPA axis compared with layer-type chicks.     

Gender-related differences of mouse liver d-aspartate oxidase in the activity and response to administration of d-aspartate and peroxisome proliferators

• 1.1. The hepatic d-aspartate oxidase activity was found to be higher in female ddY and ICR mice than in their male counterparts. On the contrary, the free d-aspartate content in the liver was lower in female mice than in male mice, suggesting that d-aspartate is actually metabolized by d-aspartate oxidase in vivo.
• 2.2. Oral administration of d-aspartate to the animals increased the hepatic d-aspartate oxidase activity 2–3 fold in both genders without any significant difference in the rate of the increase between the genders.
• 3.3. Several peroxisomal enzyme activities other than d-aspartate oxidase examined were not affected by this treatment.
• 4.4. Experiments in vitro suggested that the increase in the d-aspartate activity might be explained in part by stabilization of the enzyme by d-aspartate.
• 5.5. The administration of clofibrate, a peroxisome proliferator, to male mice, increased the hepatic d-aspartate oxidase activity with a significant simultaneous decrease of d-aspartate content in the liver, in agreement with a possible role of the enzyme n vivo.
• 6.6. On the other hand, the administration of clofibrate or dehydroepiandrosterone to female mice decreased the d-aspartate oxidase activity.
• 7.7. The peroxisome proliferators were suggested to act to eliminate the gender difference of hepatic d-aspartate oxidase activity in mice.

     

Central administration of galanin stimulates feeding behavior in chicks

Galanin is recognized as one of the orexigenic peptides in the brain of mammals and fishes. The amino acid sequence of chicken galanin and its distribution in the brain are similar to those of mammals, suggesting that the brain galanin might be related to feeding regulation in chicks. The purpose of the present study was to investigate whether intracerebroventricular (ICV) injection of galanin affected feeding behavior of chicks (Gallus gallus). The injection of galanin increased food intake of layer and broiler chicks. We also found that the galanin-induced feeding behavior was attenuated in layer chicks by the co-injection of yohimbine and beta-funaltrexamine, which are the antagonists of adrenergic alpha-2 receptor and opioid mu-receptor, respectively. It is therefore possible that the orexigenic effect of galanin is mediated by these receptors.     

Central administration of substance P inhibits feeding behavior in chicks

The purpose of the present study was to determine whether central administration of substance P (SP), a tachykinin neuropeptide, influenced feeding behavior in layer chicks (Gallus gallus). Intracerebroventricular (ICV) injections of 5 nmol SP decreased food intake in 5- and 6-day-old chicks under both ad libitum and 3-h fasting conditions. There are 3 major subtypes of tachykinin receptors, namely, neurokinin 1, 2 and 3 receptors. Injection of neurokinin A and neurokinin B, which are respectively endogenous agonists for neurokinin 2 and 3 receptors, did not suppress feeding behavior in chicks, suggesting that the anorexigenic effect of SP might be mediated by the neurokinin 1 receptor rather than neurokinin 2 and 3 receptors. Chicks that received 5 nmol SP did not change their locomotion, standing, sitting or drinking time, suggesting that its anorexigenic action might not be due to SP-induced hyperactivity or sedation. ICV injection of SP increased water intake, also indicating that SP likely did not affect feeding behavior through malaise. In addition, the anorexigenic effect of SP might not be related to corticotrophin-releasing hormone (CRH) because plasma corticosterone concentration was not affected by ICV injection of SP and co-administration of the CRH receptor antagonist astressin did not affect the anorexigenic effect of SP. The present study suggests that central SP acts as an anorexigenic neuropeptide in chicks.     

Central administration of alpha-melanocyte-stimulating hormone changes lipid metabolism in chicks

Alpha-melanocyte-stimulating hormone (MSH) is well known as an anorexigenic peptide in the brain of mammals. In addition to this, brain alpha-MSH enhances heat production (HP), indicating that the peptide acts as a catabolic factor in the regulation of energy metabolism. The anorexigenic effect of alpha-MSH is also observed in chicks (Gallus gallus), but no information has been available for its effect on HP. The present study was performed to examine whether intracerebroventricular (ICV) injection of alpha-MSH increases HP in chicks. The injection of alpha-MSH (10 and 100 pmol) did not affect oxygen consumption, carbon dioxide production and HP during the 1 h post-injection period. This result was supported by another result that ICV injection of alpha-MSH did not affect locomotion activity in chicks. In contrast, the respiratory quotient was significantly lowered by the ICV injection of MSH. We also found that alpha-MSH significantly increased plasma non-esterified fatty acid concentrations. In summary, brain alpha-MSH appears to exert generally catabolic effects on lipid metabolism in the chick, but does not appear to be involved in the regulation of HP.     

Central gastrin inhibits feeding behavior and food passage in neonatal chicks.

The gastrin/cholecystokinin (CCK) family is recognized as the principal family of hormones involved in regulation of the gastrointestinal tract CCK is recognized as a satiety hormone in mammalian species, but it has been suggested that gastrin rather CCK may have an important role in controlling feeding behavior in the neonatal chick through a poorly developed blood brain barrier. So far, however, there is no direct evidence that central gastrin inhibits food intake in neonatal chicks. The aim of this study was to elucidate whether central administration of gastrin 1) inhibits feeding behavior and 2) alters food passage from the crop. The effects of central administration of gastrin on food intake were investigated in experiment 1. Birds (2-day-old) were food-deprived for 3 h and then gastrin or saline was injected intracerebroventricularly. Gastrin strongly inhibited food intake in a dose-dependent fashion for 2 h. Thereafter, the effects of central gastrin on feeding behavior and serum corticosterone concentration were examined in experiment 2. Following central administration of gastrin, food intake was depressed and pecking behavior was inhibited. Serum corticosterone concentration was not altered by central administration of gastrin. The influence of central gastrin on food passage from the crop was investigated in experiment 3. Central administration of gastrin clearly delayed food passage. In conclusion, central gastrin appears to have a strong effect for the satiety and gastrointestinal motility in the neonatal chick.     

The social network: Neural control of sex differences in reproductive behaviors,motivation, and response to social isolation

Social animal species present a vast repertoire of social interactions when encountering conspecifics. Reproduction-related behaviors, such as mating, parental care, and aggression, are some of the most rewarding types of social interactions and are also the most sexually dimorphic ones. This review focuses on rodent species and summarizes recent advances in neuroscience research that link sexually dimorphic reproductive behaviors to sexual dimorphism in their underlying neuronal circuits. Specifically, we present a few possible mechanisms governing sexually-dimorphic behaviors, by hypothalamic and reward-related brain regions. Sex differences in the neural response to social isolation in adulthood are also discussed, as well as future directions for comparative studies with naturally solitary species.     

Central regulation of feeding behavior through neuropeptides and amino acids in neonatal chicks

Amino Acids - Animals at the neonatal stage have to eat more to support better growth and health. However, it is difficult to understand the mechanism of feeding during an early stage of life in...     

Nitric oxide synthase inhibitor attenuates the anorexigenic effect of corticotropin-releasing hormone in neonatal chicks

Nitric oxide (NO) is known as an orexigenic factor in the brain of mammals and mediates the feeding-stimulatory effect of other factors such as neuropeptide Y (NPY). In neonatal chicks, however, we recently reported that NO might have an anorexigenic effect and suggested that the feeding-regulatory mechanism in chicks might be different from that in mammals regarding NO. In the present study, we investigated the involvement of NO in the effect of other orexigenic and anorexigenic factors in neonatal chicks. Intracerebroventricular co-injection of N(G)-nitro-l-arginine methyl ester (l-NAME), a NO synthase inhibitor, did not affect NPY- and prolactin-releasing peptide-induced feeding behavior. On the other hand, the co-injection of l-NAME significantly attenuated the anorexigenic effect of corticotropin-releasing hormone (CRH). The anorexigenic effects of glucagon-like peptide-1, alpha-melanocyte-stimulating hormone and ghrelin were not affected by the l-NAME treatment. These results suggest that NO might mediate the anorexigenic effect of CRH in the brain of neonatal chicks.     

Central activation of thermogenesis by prostaglandins: dependence on CRF

Central (intracerebroventricular) injections of PGE2, PGF2 alpha caused dose dependent increases in oxygen consumption (VO2) and colonic temperature in conscious rats. The effects of combined injection of maximal doses of CRF and PGE2 were additive, whereas PGF2 alpha and CRF were not. A CRF receptor antagonist, (alpha helical CRF 9-41, 25 micrograms icv) markedly inhibited the effects of PGF2 alpha on VO2 and temperature, but did not affect the actions of PGE2. These data indicate that PGF2 alpha and PGE2 stimulate thermogenesis by two different mechanisms, the former depending on CRF release. PGF2 alpha may be involved in the thermogenic actions of interleukin-1 beta which is also a potent thermogenic agent acting via CRF.     

Different susceptibility of prefrontal cortex and hippocampus to oxidative stress following chronic social isolation stress

Chronic oxidative stress plays an important role in depression. The aim of present study was to examine the stress-induced changes in serum corticosterone (CORT) levels, cytosolic protein carbonyl groups, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO) and total superoxide dismutase (SOD) activity in the prefrontal cortex versus hippocampus of male Wistar rats exposed to acute (2 h of immobilization or cold), chronic (21d of social isolation) stress, and their combination (chronic + acute stress). The subcellular distribution of nuclear factor-κB (NF-κB) and cytosolic cyclooxygenase 2 (COX-2) protein expressions were also examined. Depressive- and anxiety-like behaviors were assessed via the forced swim, sucrose preference, and marble burying tests in chronically isolated rats. Although both acute stressors resulted in elevated CORT, increased MDA in the prefrontal cortex and NF-κB activation accompanied by increased NO in the hippocampus were detected only following acute cold stress. Chronic isolation resulted in no change in CORT levels, but disabled appropriate response to novel acute stress and led to depressive- and anxiety-like behaviors. Increased oxidative/nitrosative stress markers, likely by NF-κB nuclear translocation and concomitant COX-2 upregulation, associated with decreased SOD activity and GSH levels, suggested the existence of oxidative stress in the prefrontal cortex. In contrast, hippocampus was less susceptible to oxidative damage showing only increase in protein carbonyl groups and depleted GSH. Taken together, the prefrontal cortex seems to be more sensitive to oxidative stress than the hippocampus following chronic isolation stress, which may be relevant for further research related to stress-induced depressive-like behavior.     

Exogenous administration of octanoic acid accelerates octanoylated ghrelin production in the proventriculus of neonatal chicks

Ghrelin is modified by fatty acid at the third serine residue. In this study, derivation of fatty acid for acylation of ghrelin was investigated using a hatchling chicken model. We first studied ghrelin gene expression and production in the neonatal chick proventriculus and then investigated the effect of exogenous octanoic acid (OA) administration on acylated ghrelin production. In a free-feeding condition on day 2.5 after hatching, the density of ghrelin mRNA-expressing (ghrelin-ex) cells was greater than that of ghrelin-immunopositive (ghrelin-ip) cells, but no difference was found between those densities in adult chickens. Intraperitoneal or oral administration of OA for a few days significantly increased the density of ghrelin-ip cells without any changes in ghrelin-ex cells and elevated only octanoylated ghrelin levels in the proventriculus. The results indicate that fatty acid absorbed from food is directly utilized in acylated ghrelin production in the chicken.     

Repeated thermal conditioning during the neonatal period affects behavioral and physiological responses to acute heat stress in chicks

ObjectiveThe aim of the present study was to investigate the effects of repeated thermal conditioning (RTC) at an early age on physiological and behavioral responses in chicks.MethodsBirds were assigned to one of the four treatments in which the RTC was exposure to 40 °C for 15 min daily. The treatments were 1) no thermal conditioning (control); 2) early exposure group (EE; RTC from 2 to 4 days of age); 3) later exposure group (LE; RTC from 5 to 7 days of age); or 4) both early and later exposure (BE; RTC from 2 to 7 days of age). All groups of chicks were challenged with high ambient temperature (40 °C for 15 min) at two weeks of age.ResultsDuring heat challenge, initiation times of dissipation behaviors (panting and wing-drooping) were measured. Rectal temperature and respiration rate were measured after and before heat challenge. Hypothalamic samples and blood were collected at the end of heat challenges. Initiation times of dissipation behaviors and rectal temperature were not affected by the treatments. Increases in respiration rate in response to heat challenge were suppressed by early RTC treatment. There was no clear pattern of glucose levels in relation to thermal conditioning, whereas plasma corticosterone levels were decreased by early treatment (EE and BE groups). Hypothalamic thyrotropin releasing hormone gene expression was suppressed by early and later thermal conditioning and suppressed further by both early and later exposure. Neuropeptide Y gene expression in the BE group was lower than in the other groups, with a similar trend for corticotropin releasing hormone expression.ConclusionOur results suggest that the effect of repeated thermal conditioning on the central thermoregulatory system depends on the number of times that chicks experienced conditioning. In addition, repeated thermal conditioning has greater effects on the acquisition of thermotolerance when conditioning occurs in chicks of two to four days of age in comparison with chicks of five to seven days of age.     

The effects of adrenergic, opioid and pancreatic polypeptidergic compounds on feeding and other behaviors in neonatal leghorn chicks

The present study examined the effects of intracerebral (IC) administration of pancreatic polypeptide (PP), neuropeptide Y (NPY), norepinephrine (NE), dynorphin and naloxone on food intake in 2-day-old Leghorn chicks. Of the compounds studied, only PP (20 micrograms) and naloxone (10 and 20 micrograms) elevated food intake significantly as compared to saline injections. NPY, a potent orexigenic agent in mammals, did not elevate consumption significantly in a dose-related fashion. This latter finding was attributed to the occurrence of tonic-clonic convulsions following NPY administration. However, for those chicks which did not exhibit behavioral convulsions, food intake appeared to be elevated by 1, 5 and 10 micrograms of NPY. Similarly, NE did not elevate food intake but instead induced sedation and narcolepsy, a behavioral response which could be distinguished from the convulsions observed after NPY. In a separate group of chicks, the effect of NPY on cortical activity was examined. Bipolar electrodes were used to record EEG activity before and after IC injections of saline, NPY or NE. The behavioral convulsions induced by NPY corresponded with an increase in high amplitude sharp-wave activity, which persisted for up to 30 min post-injection. Collectively, these results suggest that the neurochemical substrates for feeding in 2-day-old Leghorn chicks are distinct from those underlying food intake in adult mammals.     

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long‐term effects of social isolation during adolescence

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long‐term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 34–46, 2016