G. Bowers et al., REGION-SPECIFIC REGULATION OF GLUTAMIC-ACID DECARBOXYLASE (GAD) MESSENGER-RNA EXPRESSION IN CENTRAL STRESS CIRCUITS, The Journal of neuroscience, 18(15), 1998, pp. 5938-5947
Neurocircuit inhibition of hypothalamic paraventricular nucleus (PVN)
neurons controlling hypothalamo-pituitary-adreno-cortical (HPA) activi
ty prominently involves GABAergic cell groups of the hypothalamus and
basal forebrain. In the present study, stress responsiveness of GABAer
gic regions implicated in HPA inhibition was assessed by in situ hybri
dization, using probes recognizing the GABA-synthesizing enzyme glutam
ic acid decarboxylase (GAD65 and GAD67 isoforms). Acute restraint pref
erentially 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 (B
ST) and hippocampus (CA1 and dentate gyrus). In all cases GAD67 mRNA p
eaked at 1 hr after stress and returned to unstimulated levels by 2 hr
. GAD65 mRNA upregulation was only observed in the BST and dentate gyr
us. In contrast, chronic intermittent stress increased GAD65 mRNA in t
he anterior hypothalamic area, dorsomedial nucleus, medial preoptic ar
ea, suprachiasmatic nucleus, anterior BST, perifornical nucleus, and p
eriparaventricular nucleus region. GAD67 mRNA increases were only obse
rved in the medial preoptic area, anterior BST, and hippocampus. Acute
and chronic stress did not affect GAD65 or GAD67 mRNA expression in t
he caudate nucleus, reticular thalamus, or parietal cortex. Overall, t
he results indicate preferential upregulation of GAD in central circui
try responsible for direct (hypothalamus, BST) or multisynaptic (hippo
campus) control of HPA activity. The distinct patterns of GAD65 and GA
D67 by acute versus chronic stress suggest stimulus duration-dependent
control of GAD biosynthesis. Chronic stress-induced increases in GAD6
5 mRNA expression predict enhanced availability of GAD65 apoenzyme aft
er prolonged stimulation, whereas acute stress-specific GAD67 upregula
tion is consistent with de novo synthesis of active enzyme by discrete
stressful stimuli.