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Brain amino acid metabolism has been reported to regulate body temperature, feeding behavior and stress response. Central injection of taurine induced hypothermic and anorexigenic effects in chicks. However, it is still unknown how the amino acid metabolism is influenced by the central injection of taurine. Therefore, the objective of this study was to investigate the changes in brain and plasma free amino acids following central injection of taurine. Five-day-old male Julia layer chicks (n = 10) were subjected to intracerebroventricular (ICV) injection with saline or taurine (5 µmol/10 µL). Central taurine increased tryptophan concentrations in the diencephalon, and decreased tyrosine in the diencephalon, brainstem, cerebellum, telencephalon and plasma at 30 min post-injection. Taurine was increased in all the brain parts after ICV taurine. Although histidine and cystathionine concentrations were increased in the diencephalon and brainstem, several amino acids such as isoleucine, arginine, methionine, phenylalanine, glutamic acid, asparagine, proline, and alanine were reduced following central injection of taurine. All amino acid concentrations were decreased in the plasma after ICV taurine. In conclusion, central taurine quickly changes free amino acid concentrations in the brain and plasma, which may have a role in thermoregulation, food intake and stress response in chicks., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

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 the brain of the rodent model. Chickens are precocial and they can look for their food by themselves right after hatching. Neonatal chicks have a relatively large-sized brain; therefore, the drugs are easy to administer centrally and changes in food intake can be clearly monitored. Sleeping status, which affects food intake, can be estimated from the posture. The closest vertebrate outgroup to mammals is birds, but it was reported that the organization of the human genome is closer to that of the chicken than the mouse. Thus, it is important to understand the central mechanism of feeding regulation in the neonatal chicks. In neuropeptides, the number of candidates as the orexigenic factor was less than those as the anorexigenic factor, even at an early growth stage. Some of the neuropeptides have reverse effects, e.g., ghrelin and prolactin releasing peptides, or no effects compared to the effects confirmed in mammals. Some of the genetic differences between meat-type (broiler) and layer-type chickens would explain the difference in food intake. On the other hand, it was difficult to explain the feeding mechanism by neuropeptides alone, as neonatal chicks have a repeated feeding, sleeping, and resting behavior within a short period. Some of the amino acids and their metabolites act centrally to regulate feeding with sedative and hypnotic effects. In conclusion, endogenous neuropeptides and endogenous and/or exogenous nutrients like amino acids collaborate to regulate feeding behavior in neonatal chicks.

In the present study, the effects of both single (6 mmol L-serine/10 ml/kg orally administrated) and chronic (2% L-serine solution freely given for 28 days) treatments on depression-like behavior were evaluated in Wistar rats, representing the control, and Wistar Kyoto rats, representing an animal model of depression. Both single and chronic L-serine treatments decreased the duration of immobility, which is an index of a depressive-like state, in the forced swimming test in both strains. However, the decreases in the duration of immobility appear to be regulated differently by the different mechanisms involved in single and chronic L-serine treatments. In the prefrontal cortex and hippocampus, single L-serine treatment increased the concentrations of L-serine, but not D-serine, while chronic L-serine treatment increased those of D-serine, but not L-serine. These data suggest that the antidepressant-like effects of single and chronic L-serine treatments may have been induced by the increased L-serine and D-serine concentrations, respectively, in the brain. In addition, chronic L-serine treatment increased cystathionine concentrations in the hippocampus and prefrontal cortex in Wistar rats, but not in Wistar Kyoto rats, suggesting that Wistar Kyoto rats have an abnormality in the serine-cystathionine metabolic pathway. In conclusion, single and chronic L-serine treatments may induce antidepressant-like effects via the different mechanisms related to serine metabolism in the brain.

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.

While abnormalities in monoamine metabolism have been investigated heavily per potential roles in the mechanisms of depression, the contribution of amino acid metabolism in the brain remains not well understood. In additional, roles of the hypothalamus-pituitary-adrenal axis in stress-regulation mechanisms have been of much focus, while the contribution of central amino acid metabolism to these mechanisms has not been well appreciated. Therefore, whether depression-like states affect amino acid metabolism and their potential roles on stress-regulatory mechanisms were investigated by comparing Wistar Kyoto rats, which display depression-like behaviors and stress vulnerability, to control Wistar rats. Brain amino acid metabolism in Wistar Kyoto rats was greatly different from normal Wistar rats, with special reference to lower cystathionine and serine levels. In addition, Wistar Kyoto rats demonstrated abnormality in dopamine metabolism compared with Wistar rats. In the case of stress response, amino acid levels having a sedative and/or hypnotic effect were constant in the brain of Wistar Kyoto rats, though these amino acid levels were reduced in Wistar rats under a stressful condition. These results suggest that the abnormal amino acid metabolism may induce depression-like behaviors and stress vulnerability in Wistar Kyoto rats. Therefore, we hypothesized that abnormalities in amino acid and monoamine metabolism may induce depression, and amino acid metabolism in the brain may be related to stress vulnerability.

Taurine, a substrate of taurine transporter, has functions as a neuromodulator and antioxidant and beta-alanine, a taurine transporter inhibitor, has a role as a neurotransmitter in the brain, and they were expected to be involved in depression-like behavior and antidepressant treatment. These facts aroused our interest in new capabilities of taurine and beta-alanine. Thus, to investigate the effects of chronic ingestion of taurine- (22.5 mmol/kg diet) supplemented diet and beta-alanine- (22.5 mmol/kg diet) supplemented diet under acute stressful conditions, behavioral changes and brain metabolites were compared with mice fed a control diet. In the open field test, no significant difference was observed in locomotor activity among groups. In the elevated plus-maze test, however, significant increases in the percentage of time spent and entries in the open arms were observed in the beta-alanine-supplemented diet fed group compared to both controls and animals fed with taurine-supplemented diet. Moreover, a significant decrease in the duration of immobility was observed in the taurine-supplemented diet group in the forced swimming test compared to both controls and animals fed with beta-alanine-supplemented diet. Taurine-supplemented diet increased taurine and L: -arginine concentrations in the hypothalamus. In contrast, beta-alanine-supplemented diet decreased the concentration of 5-hydroxyindoleacetic acid, a major metabolite of serotonin, in the hypothalamus. Beta-alanine-supplemented diet also increased carnosine (beta-alanyl-L: -histidine) concentration in the cerebral cortex and hypothalamus, and brain-derived neurotrophic factor concentration in the hippocampus. These results suggested that taurine-supplemented diet had an antidepressant-like effect and beta-alanine-supplemented diet had an anxiolytic-like effect.

Glutamate, an excitatory amino acid, acts at several glutamate receptor subtypes. Recently, we reported that central administration of glutathione induced hypnosis under stressful conditions in neonatal chicks. Glutathione appears to bind to the N-methyl-D-aspartate (NMDA) receptor. To clarify the involvement of each glutamate receptor subtype during stressful conditions, intracerebroventricular (i.c.v.) injection of several glutamate receptor agonists was given to chicks under social separation stress. Glutamate dose-dependently induced a hypnotic effect. NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate are characterized as ionotropic glutamate receptors (iGluRs). Although NMDA also induced a sedative effect, [corrected] the potency of NMDA for sleep-like behavior [corrected] was less than that of glutamate. AMPA tended to decrease distress vocalizations induced by acute stress and brought about a sedative effect. Kainate and (S)-3, 5-dehydroxyphenylglycine, which is a metabotropic glutamate receptor agonist, had no influence on chick behavior. Thus, it is suggested that the iGluRs, NMDA and AMPA, are important in inducing hypnosis and sedation under acute stress in chicks.

Recently, we reported that intracerebroventricular (i.c.v.) injection of L-alanine attenuated the stress response under an acute stressful condition in chicks. However, no information of L-alanine was available for the influence on energy expenditure and changes in the posture under stressful conditions. The purpose of the present study was to clarify whether central L-alanine affects heat production (HP) of neonatal chicks, and whether HP is correlated with the behavior after isolation-induced stress. The i.c.v. injection of L-alanine (0.8 micromol) decreased oxygen consumption, carbon dioxide production and HP shortly after injection. Central L-alanine reduced the posture for active wakefulness, but increased the posture for sitting motionless with head drooped (sleeping posture). The present study demonstrates that central L-alanine decreases energy expenditure and causes a hypnotic effect in chicks exposed to an acute stressful condition.