Ventral Hippocampal CA1 GADD45B Regulates Susceptibility to Social Stress by Influencing NMDA Receptor-Mediated Synaptic Plasticity
Mengbing Huang1 · Jian Bao1 · Xiaoqing Tao1 · Yifan Niu1 · Kaiwei Li1 · Ji Wang1 · Xiaokang Gong1 · Rong Yang1 · Yuran Gui1 · Hongyan Zhou1 · Yiyuan Xia1 · Youhua Yang1 · Binlian Sun1 · Wei Liu1 · Xiji Shu11 Hubei Key Laboratory of Cognitive and Afective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan 430056, China
Abstract
Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Keywords
Chronic stress; Ventral hippocampal CA1; GADD45B; NMDA receptor; Synaptic plasticity
