title: GluR5-mediated glutamate signaling regulates hypothalamo-pituitary-adrenocortical stress responses at the paraventricular nucleus and median eminence.
abstract: Glutamate is the main excitatory neurotransmitter in the central nervous system, and plays an excitatory role in generation of hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. The current study assesses the role of kainate-preferring receptors in glutamatergic excitation of the HPA axis. In situ hybridization and immunohistochemical analyses confirmed the existence of the GluR5 kainate subunit in the paraventricular nucleus of the hypothalamus (PVN). Importantly, GluR5 immunoreactivity was enriched in the external lamina of the median eminence, where it is co-localized with corticotropin releasing hormone (CRH). Intra-PVN infusion of LY382884 increased plasma adrenocorticotropin (ACTH), corticosterone and PVN c-Fos immunoreactivity. Infusions of LY382884 into the median eminence region, on the other hand, reduced restraint induced ACTH release without altering c-Fos expression. Together, these findings provide evidence for glutamate-mediated signaling in control of CRH release at the PVN and median eminence, mediated by way of kainate-preferring receptor complexes.
authors.affiliation: University of Cincinnati Graduate Program in Neuroscience, Cincinnati, OH, United States of America. evansonk@email.uc.edu
authors.forename: Nathan K
authors.initials: NK
authors.lastname: Evanson
authors.forename: Daniella C
authors.initials: DC
authors.lastname: Van Hooren
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000097:blood; D018698:Glutamic Acid / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D008845:Microinjections; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D018698:Glutamic Acid; D007546:Isoquinolines; D016760:Proto-Oncogene Proteins c-fos; D018092:Kainic Acid Receptors; C400802:LY382884