Abstract

Depression is one of the most common mental disorders with an increasing incidence. However, factors involved in depression are so complex, thus it is difficult to find effective strategies to reverse the impairments. This study aims to verify the role of regulator of G protein signaling 2 (RGS2) in the mouse mode of unpredictable mild stress-induced depression-like behaviors. Knockdown of RGS2 was achieved by transfection of siRNA-RGS2 in mouse hippocampal (HT-22) cells in vitro and injection of recombinant adenovirus expressing siRNA-RGS2 in mice in vivo . An aberrant high expression of RGS2 was found in mice with depression-like behaviors through immunohistochemical analysis. Silencing of RGS2 or Forskolin (activator of cAMP pathway) developed sweet water consumption, reduced inflammation and oxidative stress injury, and attenuated cognitive impairment and neuronal damage in mice with depression-like behaviors. Furthermore, regeneration was enhanced and apoptosis was repressed in mouse hippocampal neurons in the presence of RGS2 knockdown and Forskolin. Mechanistic studies indicated that silencing of RGS2 promoted the activation of cAMP pathway, thus rescuing depression-like behaviors of mice. Collectively, our study uncovered the role of RGS2-dependent cAMP pathway in regulation of cognitive impairment and hippocampal neuron regeneration in depression-like behaviors of mice, which may be a potential therapeutic target for impairments and symptoms associated with depression.