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 (- /-). 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.
Keywords: Corticosterone, hypothalamic paraventricular nucleus, hypothalamic – pituitary – adrenal axis, medial amygdala, PACAP, stress
The Journal club provoked much discussion and interaction considering why PACAP should be considered as a key factor at all. Some of the immunofluorescence staining and immunohistochemistry results seemed contentious. The classification of open-field and restraint stress as emotional stressors, ether inhalation(for 90 seconds) as a physical stressor and cold exposure (4 degree Celsius) as a metabolic stressor was new and somewhat surprising. Shilpa handled the many questions that were posed about the paper and also provided a detailed critique of several of the discussion items as they seem to contradict findings in multiple papers.