Faculty Collaboration Database

Region-specific regulation of glutamic acid decarboxylase (GAD) mRNA expression in central stress circuits. J Neurosci 1998 Aug 01;18(15):5938-47

Date

07/22/1998

Pubmed ID

9671680

Pubmed Central ID

PMC6793042

DOI

10.1523/JNEUROSCI.18-15-05938.1998

Scopus ID

2-s2.0-17344363638 (requires institutional sign-in at Scopus site)   223 Citations

Abstract

Neurocircuit inhibition of hypothalamic paraventricular nucleus (PVN) neurons controlling hypothalamo-pituitary-adrenocortical (HPA) activity prominently involves GABAergic cell groups of the hypothalamus and basal forebrain. In the present study, stress responsiveness of GABAergic regions implicated in HPA inhibition was assessed by in situ hybridization, using probes recognizing the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD65 and GAD67 isoforms). Acute restraint preferentially increased GAD67 mRNA expression in several stress-relevant brain regions, including the arcuate nucleus, dorsomedial hypothalamic nucleus, medial preoptic area, bed nucleus of the stria terminalis (BST) and hippocampus (CA1 and dentate gyrus). In all cases GAD67 mRNA peaked at 1 hr after stress and returned to unstimulated levels by 2 hr. GAD65 mRNA upregulation was only observed in the BST and dentate gyrus. In contrast, chronic intermittent stress increased GAD65 mRNA in the anterior hypothalamic area, dorsomedial nucleus, medial preoptic area, suprachiasmatic nucleus, anterior BST, perifornical nucleus, and periparaventricular nucleus region. GAD67 mRNA increases were only observed in the medial preoptic area, anterior BST, and hippocampus. Acute and chronic stress did not affect GAD65 or GAD67 mRNA expression in the caudate nucleus, reticular thalamus, or parietal cortex. Overall, the results indicate preferential upregulation of GAD in central circuitry responsible for direct (hypothalamus, BST) or multisynaptic (hippocampus) control of HPA activity. The distinct patterns of GAD65 and GAD67 by acute versus chronic stress suggest stimulus duration-dependent control of GAD biosynthesis. Chronic stress-induced increases in GAD65 mRNA expression predict enhanced availability of GAD65 apoenzyme after prolonged stimulation, whereas acute stress-specific GAD67 upregulation is consistent with de novo synthesis of active enzyme by discrete stressful stimuli.

Author List

Bowers G, 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

Acute Disease
Animals
Chronic Disease
Glutamate Decarboxylase
Hypothalamo-Hypophyseal System
Isoenzymes
Male
Neural Inhibition
Neural Pathways
Pituitary-Adrenal System
RNA, Messenger
Rats
Rats, Sprague-Dawley
Stress, Physiological
Synaptic Transmission