166,167 The CeA exerts its regulatory effects on the HPA axis through intermediary neurons in the brain stem.139 Afferent projections from the CeA densely innervate the NTS and parabrachial nucleus.92,168 The MeA sends a limited number of direct projections to the parvocellular division of the PVN169; however, this subnucleus innervates a number of nuclei that directly innervate the PVN. Neurons of the MeA project to the BNST, MePO, and ventral premammillary nucleus.169 The amygdala Inhibitors,research,lifescience,medical is a target for circulating glucocorticoids and the CeA

and MeA express both GR and MR. In contrast to the effects on hippocampal and cortical neurons, glucocorticoids increase expression of CRF in the CeA and potentiate autonomic responses to chronic stressors. find more Glucocorticoid infusion into the CeA does not acutely effect HPA activation but may play a feed-forward role to potentiate HPA responses to stress.139,157,170 Sympathetic Inhibitors,research,lifescience,medical circuits and the stress response Activation of brain stem noradrenergic neurons and sympathetic andrenomedullary circuits further contribute to the body’s response to stressful stimuli. Similarly to the HPA axis, stress-evoked activation of these systems promotes the mobilization of resources to compensate for adverse effects of stressful stimuli.3,171 The locus coeruleus (LC) contains the largest cluster

of noradrenergic neurons in the Inhibitors,research,lifescience,medical brain and innervates large segments of the neuroaxis.172 The LC has been implicated Inhibitors,research,lifescience,medical in a wide array of physiological and behavioral functions including emotion, vigilance, memory, and adaptive

responses to stress.173-175 A wide array of stressful stimuli activate LC neurons, alter their electrophysiological activity, and induce norepinephrine release.176-178 Stimulation of the LC elicits several stressassociated responses including ACTH release,179 anxiogenic-like behaviors,180 and suppression of immune functions.181 In addition, there are interactions between CRF and NE neurons in the CNS. Central administration of CRF alters activity Inhibitors,research,lifescience,medical of LC neurons and NE catabolism in terminal regions.13,182 Finally, dysfunction of catecholamergic neurons in the LC has been implicated in the pathophysiology of affective and stress-related disorders.183,184 Conclusions Maintenance of homeostasis in the presence of real or perceived challenges requires activation of a complex range of responses involving PAK6 the endocrine, nervous, and immune systems, collectively known as the stress response. Inappropriate regulation of the stress response has been linked to a wide array of pathologies including autoimmune disease, hypertension, affective disorders, and major depression. In this review we briefly discussed the major neuronal and endocrine systems that contribute to maintenance of homeostasis in the presence of stress.