江汉大学舒细记等研究人员合作发现，腹侧海马CA1区域GADD45B通过影响NMDA受体介导的突触可塑性，调节对社会压力的易感性。2024年11月27日，《神经科学通报》杂志在线发表了这项成果。

研究人员发现，压力易感小鼠的腹侧海马CA1区域（vCA1）中生长停滞DNA损伤诱导蛋白45β（GADD45B）的表达显著降低，而在背侧海马CA1（dCA1）中没有变化。此外，研究人员还证明了GADD45B负向调节腹侧海马CA1（vCA1）区域的社会压力易感性和NMDA受体依赖的长期增强（LTP）。

更重要的是，通过使用NMDA受体拮抗剂MK801进行药理学抑制，研究人员进一步提供了证据，支持GADD45B可能通过影响NMDA受体介导的LTP来调节社会压力易感性的假设。综合来看，这些结果表明，NMDA受体介导的突触可塑性的调节是GADD45B调控社会压力易感性的关键机制。

研究人员表示，GADD45B已被报道为一种活性DNA去甲基化的调控因子，并与突触可塑性和慢性压力相关的精神病理过程的调节有关。然而，它在压力易感性中的确切作用和作用机制仍然不清楚。

附：英文原文

Title: Ventral Hippocampal CA1 GADD45B Regulates Susceptibility to Social Stress by Influencing NMDA Receptor-Mediated Synaptic Plasticity

Author: 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

Issue&Volume: 2024-11-27

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.

DOI: 10.1007/s12264-024-01325-9

Source: https://link.springer.com/article/10.1007/s12264-024-01325-9