Depressive-like behaviors induced by chronic cerebral hypoperfusion associate with a dynamic change of GABAB1/B2 receptors expression in hippocampal CA1 region

Abstract

Cerebral ischemia could induce depressive-like behaviors; however, the alteration of gamma-aminobutyric acid receptors type B (GABA_B) receptors in these pathological processes has not been extensively investigated. The aim of the current study was to document the behavioral change and the alteration of GABA_B receptors in chronic cerebral hypoperfusion. The permanent occlusion of the bilateral common carotid arteries (two-vessel occlusion, 2VO) was performed to induce chronic cerebral ischemia (CCH). The depressive-like behaviors were evaluated with sucrose preference test, novelty suppress feeding test as well as forced swim test at 4, 8, and 12 weeks after the 2VO surgery. The total, surface and intracellular expressions of GABA_B subunit 1 (GABA_B1) and subunit 2 (GABA_B2) in hippocampal CA1 were quantified by western blot. The depressive-like behaviors were observed in rats suffered from 4, 8, and 12 weeks 2VO in sucrose preference test, novelty suppress feeding test and forced swim test. In addition, the surface and total expression of GABA_B1 in CA1 was reduced at 4 weeks after 2VO rather than 8 or 12 weeks. While the surface and total expression of GABA_B2 in CA1 was decreased throughout the ischemia timeline (4, 8, and 12 weeks). Taken together, our findings suggested the potential roles of GABA_B1 and GABA_B2 subunits involved in depressive-like behaviors caused by chronic cerebral hypoperfusion.

Keywords: Depressive-like behaviors; GABA(B1) subunits; GABA(B2) subunits; Hippocampal CA1 region; Two-vessel occlusion.