[show abstract][hide abstract] ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic-pituitary-adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP⁻/⁻). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP⁻/⁻ mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP⁻/⁻ and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP⁻/⁻ mice. In the PVN of PACAP⁻/⁻ mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors.
[show abstract][hide abstract] ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a peptidergic neurotransmitter that is expressed in high levels in nervous systems. Here, we investigated the roles of PACAP in autonomic system regulation by evaluating the changes caused in the autonomic nerve activities after injecting PACAP into the central nervous system (CNS) and examining stress-induced blood glucose changes in PACAP-deficient (PACAP-/-) mice. Renal sympathetic nerve activity (RSNA), blood pressure, and heart rate were elevated after injecting PACAP into the third cerebral ventricle (3CV). Similarly, other sympathetic nerve activities, including adrenal sympathetic nerve activity (ASNA), celiac sympathetic nerve activity (CSNA), and brown adipose tissue sympathetic nerve activity (BAT-SNA), were accelerated by PACAP injection. In contrast, injecting PACAP into 3CV significantly suppressed parasympathetic nerve activities, including gastric vagal nerve activity (GVNA) and celiac vagal nerve activity (CVNA). In addition, blood glucose elevations induced by stress, such as immobilization or ether exposure, were disrupted in PACAP-/- mice, although basal glucose levels in mutants were comparable to that in wild-type mice. These results suggest that CNS PACAP regulates autonomic function by maintaining a sympathetic-parasympathetic balance and contributes to peripheral homeostatic maintenance, especially under conditions of stress.