Faculty Collaboration Database

Organization and regulation of paraventricular nucleus glutamate signaling systems: N-methyl-D-aspartate receptors. J Comp Neurol 2005 Mar 28;484(1):43-56

Date

02/18/2005

Pubmed ID

15717303

DOI

10.1002/cne.20445

Scopus ID

2-s2.0-14644391614 (requires institutional sign-in at Scopus site)   81 Citations

Abstract

Stress activation of the hypothalamo-pituitary-adrenocortical (HPA) axis is mediated in part by glutamatergic neurotransmission. The precise nature of glutamate effects on stress-integrative hypothalamic paraventricular nucleus (PVN) neurons remains to be determined. Therefore, the current study was designed to delineate the organization of glutamate/NMDA receptor systems in the PVN and to assess regulation of PVN glutamate receptor subunit expression by chronic intermittent stress and glucocorticoids. Immunohistochemical studies verified that N-methyl-D-aspartate (NMDA) receptor subunit proteins NR1 and NR2A/2B are expressed in the medial parvocellular PVN, indicating the potential for NMDA receptor regulation of corticotropin-releasing hormone (CRH) release. Dual-label confocal analysis revealed that CRH neurons are apposed by vesicular glutamate transporter 2 (VGLUT2)-containing terminals, consistent with glutamatergic innervation from hypothalamus and/or brainstem. In situ hybridization analysis revealed a significant and selective stress-induced decrease (37%) in NR2B subunit mRNA expression in the CRH-containing region of the PVN. No changes were observed for NR1 or NR2A mRNAs. In contrast, none of the subunits investigated showed altered expression following adrenalectomy with or without low/high-dose corticosterone replacement. Thus, the observed stress regulation is likely mediated by neurogenic mechanisms in the PVN and upstream stress-transducing neurocircuitry. Because a loss of NR2B subunit inclusion in NR receptors would likely confer increased Ca(++) conductance and faster deactivation kinetics, the stress-induced decrease in NR2B mRNA is consistent with enhanced glutamate signaling in the PVN following chronic stress and, perhaps, increased basal HPA activity and more rapid and/or more robust HPA responses to stress.

Author List

Ziegler DR, Cullinan WE, Herman JP

Author

William E. Cullinan PhD Adjunct Associate Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenalectomy
Animals
Glucocorticoids
Glutamic Acid
Image Processing, Computer-Assisted
Immunohistochemistry
In Situ Hybridization
Male
Membrane Transport Proteins
Paraventricular Hypothalamic Nucleus
Radioimmunoassay
Rats
Rats, Sprague-Dawley
Receptors, Glutamate
Receptors, N-Methyl-D-Aspartate
Signal Transduction
Stress, Psychological
Vesicular Glutamate Transport Protein 1
Vesicular Glutamate Transport Protein 2