Regulation of Hypothalamo-Pituitary-Adrenocortical Responses to Stressors by the Nucleus of the Solitary Tract/Dorsal Vagal Complex

• Published in: Cellular and molecular neurobiology Vol. 38; no. 1; pp. 25 - 35
• Main Author: Herman, James P.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2018; Springer Nature B.V
• Subjects: Adrenal Cortex - drug effects; Adrenal Cortex - metabolism; Adrenal glands; Adrenocorticotropic hormone; Animals; Aortic Bodies - drug effects; Aortic Bodies - metabolism; Biomedical and Life Sciences; Biomedicine; Cell Biology; Corticosterone; Corticosterone - metabolism; Corticosterone - pharmacology; Corticotropin-releasing hormone; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide 1 - metabolism; Glucagon-Like Peptide 1 - pharmacology; Glutamic Acid - metabolism; Glutamic Acid - pharmacology; Hindbrain; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - physiology; Neurobiology; Neurosciences; Norepinephrine; Paraventricular nucleus; Pituitary; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - physiology; Review Paper; Solitary Nucleus - drug effects; Solitary Nucleus - metabolism; Solitary tract nucleus; Stress, Psychological - metabolism; Stress, Psychological - psychology; Vagus nerve; Glucagon-like peptide-1; Norepinephrine; Paraventricular nucleus; Glucocorticoids; Corticotropin-releasing hormone; Prolactin-releasing peptide
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-017-0543-8

Hindbrain neurons in the nucleus of the solitary tract (NTS) are critical for regulation of hypothalamo-pituitary-adrenocortical (HPA) responses to stress. It is well known that noradrenergic (as well as adrenergic) neurons in the NTS send direct projections to hypophysiotropic corticotropin-releasing hormone (CRH) neurons and control activation of HPA axis responses to acute systemic (but not psychogenic) stressors. Norepinephrine (NE) signaling via alpha1 receptors is primarily excitatory, working either directly on CRH neurons or through presynaptic activation of glutamate release. However, there is also evidence for NE inhibition of CRH neurons (possibly via beta receptors), an effect that may occur at higher levels of stimulation, suggesting that NE effects on the HPA axis may be context-dependent. Lesions of ascending NE inputs to the paraventricular nucleus attenuate stress-induced ACTH but not corticosterone release after chronic stress, indicating reduction in central HPA drive and increased adrenal sensitivity. Non-catecholaminergic NTS glucagon-like peptide 1/glutamate neurons play a broader role in stress regulation, being important in HPA activation to both systemic and psychogenic stressors as well as HPA axis sensitization under conditions of chronic stress. Overall, the data highlight the importance of the NTS as a key regulatory node for coordination of acute and chronic stress.