Effects of Restraint Stress on Components of Adenylyl Cyclase Signal Transduction in the Rat Hippocampus

Abstract

Chronic stress can injure hippocampal neurons as well as alter hippocampal function. The adenylyl cyclase (AC) signal transduction system is an important modulator of neurotransmission in this brain region. This study was conducted to begin to understand the effects of chronic stress on the hippocampal AC system. To assess dependence of type I and type II AC mRNA expression on adrenal integrity, total RNA was prepared from the hippocampus of nonstressed rats 7 days following either sham surgery or adrenalectomy (ADX). Adrenalectomy resulted in a 60% diminution in steady-state expression of type II AC mRNA (p <. 005) and a nonsignificant fall in type I AC mRNA expression. Both sham and adrenalectomized rats were then exposed to 1-hour sessions of restraint, twice per day (0800 to 0900 and 1500 to 1600 hours) for 4 days. Following the stress paradigm, RNA was prepared from the hippocampus and type I and type II AC mRNA levels determined by Northern blot. Densitometic analysis showed that in comparison to unstressed sham rats, stressed sham rats had a significant twofold increase in steady-state levels of type I and type II mRNA. Stressed adrenalectomized rats also had increased expression in type II AC mRNA but no significant stress-induced change in expression of type I AC mRNA. To assess dependence of hippocampal membrane G-Proteins on adrenal integrity, hippocampal membranes from nonstressed rats 7 days following either sham surgery or adrenalectomy (ADX) were analyzed by immunoblot. Adrenalectomy resulted in a 25% diminution in membrane Gsα content (p <. 05), but ADX did not significantly change membrane Gi(1)α, Gi(2)α, Gβ₃₆ or Goα content. In Sham animals, the stress paradigm resulted in increased levels of membrane Gsα, Goα and Gβ. Adrenalectomy blocked the effects of stress on these G-protein changes. Restraint stress did not modulate the levels of Gi(1)α or Gi(2)α. Restraint stress induced a small but significant increase in both AC activity and cAMP levels in hippocampus of both sham and adrenalectomized rats. In summary, components of the hippocampal AC signal transduction system and Goα are modulated by factors released during stress.

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