Huang Mengbing, Bao Jian, Tao Xiaoqing, Niu Yifan, Li Kaiwei, Wang Ji, Gong Xiaokang, Yang Rong, Gui Yuran, Zhou Hongyan, Xia Yiyuan, Yang Youhua, Sun Binlian, Liu Wei, Shu Xiji
Hubei Key Laboratory of Cognitive and Affective Disorders, Institutes of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, China.
Neurosci Bull. 2025 Mar;41(3):406-420. doi: 10.1007/s12264-024-01325-9. Epub 2024 Nov 27.
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.
生长停滞DNA损伤诱导蛋白45β（GADD45B）据报道是活性DNA去甲基化的调节因子，并与突触可塑性和慢性应激相关的精神病理过程的调节有关。然而，其在应激易感性中的精确作用和作用机制仍不清楚。在本研究中，我们发现应激易感小鼠腹侧海马CA1（vCA1）而非背侧海马CA1（dCA1）中的GADD45B表达显著降低。此外，我们证明GADD45B负向调节腹侧海马CA1（vCA1）对社会应激和NMDA受体依赖性长时程增强（LTP）的易感性。重要的是，通过使用NMDA受体拮抗剂MK801进行药理学抑制，我们提供了进一步的证据支持以下假设：GADD45B可能通过影响NMDA受体介导的LTP来调节对社会应激的易感性。总体而言，这些结果表明，NMDA受体介导的突触可塑性调节是GADD45B调节对社会应激易感性的关键机制。
