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Flagellin (Flg) is a globular protein, found in bacterial flagella, that serves as a pathogen-associated molecular pattern and also serves as a toll-like receptor-5 (TLR5) ligand in vertebrates. Most ligands for TLRs are involved in non-specific effects such as anorexia and hypoactivity in an animal infected by bacteria. However, there is little knowledge on the effects of Flg in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of Flg affects food intake, voluntary activity, cloacal temperature, crop emptying rate, blood constituents, and splenic gene expression of cytokines in chicks (Gallus gallus). The effect of Flg22, an N-terminus fragment of Flg, was also investigated. IP injection of 10 µg Flg significantly increased the splenic gene expression of interleukin-8, interferon-γ (IFN-γ), and tumor necrosis factor-like cytokine-1A, suggesting that Flg activated the innate immune system in chicks. The injection of Flg significantly decreased food intake, voluntary activity, blood glucose concentration, and crop emptying rate, and increased cloacal temperature and plasma concentrations of nitrite, nitrate, and corticosterone. However, the injection of Flg22 only affected the splenic gene expression of IFN-γ, indicating that the full-length of Flg is required for its action. These results suggest that Flg, a ligand for TLR5, is related to non-specific symptoms including anorexia, hypoactivity, increase in body temperature, disturbance of food passage in the digestive tract, and the activation of hypothalamic-pituitary-adrenal axis during bacterial infection in chicks.

Mesotocin (MT) and arginine-vasotocin (AVT) are posterior pituitary derived hormones in birds and are homologous to mammalian oxytocin (OT) and vasopressin (VP), respectively. We previously reported that intracerebroventricular (ICV) injection of both MT and AVT inhibit feeding and induce wing-flapping in chicks (Gallus gallus). Because both peptides cause similar effects suggests that they might act via common receptors. However, the specific receptors of MT and AVT which mediate their anorexigenic effect have not been clarified in chicks. Thus, the purpose of the present study was to identify the receptor subtypes involved in MT- and AVT-induced anorexia and behavioral patterns by using several agonists. ICV injection of vasopressin-1 receptor agonist (V1R) (homologous to chicken AVT receptor-2 and -4 [VT2R and VT4R, respectively]), significantly decreased food intake while agonists of vasopressin-2 receptor (V2R) and OT receptor (OTR) (homologues of chicken AVT receptor-1 and MT receptor respectively) had no effect. In addition, V1R agonist induced wing-flapping although this was not affected by V2R or OTR agonists. Since VT2R has not been found in the brain of chicks, the present study suggested that VT4R might be related to the anorexigenic effect and wing-flapping induced by MT and AVT in chicks.

Selective breeding has caused striking phenotypic differences among chickens. For example, the broiler, a fast-growing phenotype, is a relatively heavy bird selected for meat production while the layer, a slower-growing, lighter bird, was developed for egg production. Broilers are prone to early obesity and show physiological and behavioural differences in response to stressors compared with layers. However, the genetic causes of the differences in the responses to stressors between them have not been determined. The purpose of the present study was to compare the ontogeny of the corticotropin-releasing hormone (CRH) system between broilers and layers, because the CRH system plays a major role in regulating stress. We found that fast-growing broilers showed significantly lower levels of diencephalic CRH mRNA expression at post-hatch days 8 and 15 and pituitary CRH receptor 1 mRNA expression from the embryonic to post-hatch stage than slower-growing layers. However, a significantly higher level of CRH-binding protein (CRH-BP), which inactivates CRH and prevents pituitary-adrenal stimulation, was found in broilers compared with layers. Indeed, broilers showed significantly lower levels of plasma corticosterone (CORT) than layers. Subjecting birds to isolation stress did not alter the CORT level of broilers, but increased that of layers. Collectively, the stress-coping actions of the CRH system via the hypothalamic-pituitary-adrenal (HPA) axis might be less responsive in broilers than in layers due to differential gene expression. Together, the present results provide evidence that genetic selection has altered gene expression in the CRH system of the fast-growing broiler, causing blunted HPA axis activity in response to stressors.

Corticotrophin-releasing hormone (CRH) plays an important role in response to stress, and exerts a physiological effect via its receptor, CRH receptor type-1 (CRH-R1) and CRH receptor type-2 (CRH-R2) with high affinity to CRH-R1 in mammals. Urocortin-3 (UCN-3), a CRH family peptide, is an endogenous ligand for CRH-R2 in mammals. The physiological roles of UCN-3 and CRH-R2 have been investigated in mammals, although their roles still need to be clarified in chicks (Gallus gallus). Few studies have been performed comparing the physiological responses of CRH and UCN-3 in chicks. Therefore the present study was conducted to investigate the effect of intracerebroventricular (ICV) injection of UCN-3 on food intake, rectal temperature, crop-emptying rate and behaviors in chicks, and to compare these physiological responses with the effects resulting from CRH injection. The ICV injection of 20 and 80 pmol UCN-3 decreased food intake, increased rectal temperature and decreased crop-emptying rate and the results were similar to those achieved with CRH. The injection of both UCN-3 and CRH increased spontaneous activity but the behavioral patterns were different: CRH increased the number of vocalizations while UCN-3 increased the number of jumps, wing-flaps and scratching behaviors. These results suggest that UCN-3 regulates food intake, body temperature, and gastric emptying via the CRH-R2 in the brain of chicks, and these effects were similar to those induced by CRH.

Mast cells are a type of immune cell widely distributed in the body of vertebrates. Mast cells have many granules that contain several bioactive molecules such as histamine, and these molecules are released through degranulation when the mast cell receives certain stimuli. Because the number of mast cells increases during infection in chickens (Gallus gallus), the activity of mast cells might be related to non-specific symptoms such as anorexia under an infectious condition. Therefore, the purpose of the present study was to investigate whether intraperitoneal (IP) and intracerebroventricular (ICV) injections of compound 48/80, which induces degranulation of mast cells, affects feeding, voluntary activity, cloacal temperature, and the concentrations of plasma corticosterone (CORT) and glucose in chicks. The effect of histamine, which is found in mast cell granules, on these parameters was also investigated. IP injection of compound 48/80 significantly decreased food intake, voluntary activity, and cloacal temperature, and increased plasma CORT concentration in the chicks. While ICV injection of compound 48/80 also decreased food intake, it increased cloacal temperature and plasma glucose concentration. Both IP and ICV injections of histamine significantly decreased food intake, cloacal temperature, and plasma CORT concentration. However, only IP injection of histamine significantly decreased voluntary activity and increased plasma glucose concentration. The results suggest that degranulation of mast cells is related to non-specific symptoms in chicks, although the mechanism seems to be different between peripheral and central tissues. In addition, the effect of peripherally-injected compound 48/80 may be partly mediated by histamine.