.. Brain stem neurons Brain stem catecholaminergic centers play an important role in the Chk2 phosphorylation regulation of the HPA axis. Neurons of the nucleus of the solitary tract (NTS) relay sensory information to the PVN from cranial nerves that innervate large areas of thoracic and abdominal viscera. The NTS also receives projections from limbic structures that regulate behavioral responses to stress including the medial prefrontal cortex and the central nucleus of the Inhibitors,research,lifescience,medical amygdala.92 Accordingly, neuronal populations in the NTS are activated following lipopoly saccharide injection,93,94 hypotension,95 forced

swim, and immobilization stress paradigms.96 Stress-receptive neurons in the A2/C2 region of the NTS densely innervate the medial parvocellular subdivision of the PVN.97,98 Findings from both in vivo and in vitro studies demonstrate that catecholaminergic input represents a major excitatory

drive on the HPA axis and induces Inhibitors,research,lifescience,medical CRF expression and protein release through an α-1 adrenergic receptor-dependent mechanism.99-101 Nonaminergic NTS neurons also innervate the Inhibitors,research,lifescience,medical PVN and contribute to HPA axis regulation. Glucagon-like peptide 1 containing neurons in the NTS are activated by physiological stressors and have been shown to induce ACTH release in vivo.102,103 The neuropeptides somatostatin, substance P, and enkephalin are also expressed in NTS neurons that innervate the PVN and have been shown to have regulatory effects on the HPA axis.104-106 The lamina terminals A series of interconnected cell groups including the subfornical organ (SFO), median preoptic nucleus (MePO), and the vascular organ of the lamina terminalis are localized

Inhibitors,research,lifescience,medical on the rostral border of the third ventricle and make up the lamina terminalis.107 Cell groups of the lamina terminalis lie outside of the blood-brain Inhibitors,research,lifescience,medical barrier and relay information concerning the osmotic composition of blood to the PVN.108 The medial parvocellular subdivision of the PVN receives rich innervation from the SFO and to a lesser extent from the OVLT and MePO.109 Neurons in the SFO that project to the PVN are angiotensinergic, and promote CRF secretion and biosynthesis.110,111 This afferent pathway has parallel input to the magnocellular division of the PVN, and had been hypothesized to serve as a link between HPA and neurohypophysial activation.112,114 Hypothalamus The medial parvocellular Methisazone subdivision of the PVN receives afferent projections from y-aminobutyric acid (GABA)-ergic neurons of the hypothalamus.115 Hypophysiotropic neurons of the PVN express GABA-A receptor subunits116 and hypothalamic injection of the GABA-A receptor agonists inhibit glucocorticoid secretion following exposure to stressors.117,118 These studies suggest that GABA plays a prominent role in hypothalamic stress integration.