Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm
Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm
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DOI：
10.1186/s13041-019-0488-6
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发表时间：
2019-08-02
期刊：
影响因子：
3.6
通讯作者：
Kida, Satoshi
中科院分区：
文献类型：
--
作者：
Ishikawa, Rie;Uchida, Chiaki;Kida, Satoshi
创伤后应激障碍（PTSD）是一种与创伤经历记忆相关的精神疾病。最近的研究表明，情境恐惧记忆的遗忘是通过神经发生增强剂（例如美金刚（MEM）和运动）诱导的成人海马神经发生的增加而促进的，这提高了神经发生增强剂通过促进创伤记忆的遗忘来改善创伤后应激障碍（PTSD）的可能性。另一方面，攻击性小鼠反复暴露于社交失败（SD）压力会诱发攻击性小鼠的社交回避行为和慢性焦虑样行为。在这项研究中，我们假设这种 SD 应激范式是一个 PTSD 样模型，并检查了神经发生增强剂 MEM 治疗对 SD 应激诱导的 PTSD 样行为的影响。雄性 C57BL/6 小鼠连续 10 天接受 SD 应激，并使用社交互动和升高的零迷宫任务评估对攻击者的社交回避记忆（攻击者小鼠的记忆）和焦虑样行为。与之前的研究一致，SD 小鼠形成了社交回避记忆，并表现出增加的焦虑样行为。重要的是，随后的 MEM 治疗（每周一次，持续 4 周）显着减少了社交回避行为，表明 MEM 治疗的 SD 小鼠表现出社交回避记忆的遗忘。有趣的是，经 MEM 处理的 SD 小鼠表现出与未暴露于 SD 应激的对照小鼠类似的焦虑样行为。此外，MEM治疗的SD小鼠在再次接触攻击者后没有表现出社交回避记忆的恢复。我们的研究结果表明，神经发生增强剂不仅可以增强对创伤记忆的遗忘，还可以改善类似 PTSD（焦虑）的行为。
Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Recent studies have shown that the forgetting of contextual fear memory is promoted via increased adult hippocampal neurogenesis induced by neurogenesis enhancers, such as memantine (MEM) and exercise, raising the possibility that neurogenesis enhancers improve PTSD by facilitating the forgetting of traumatic memory. On the other hand, repeated exposure to social defeat (SD) stress by aggressor mice induces social avoidance behavior to the aggressor and chronic anxiety-like behavior. In this study, we assumed this SD stress paradigm as a PTSD-like model and examined the effects of treatment with neurogenesis enhancer MEM on SD stress-induced PTSD-like behavior. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. Consistent with previous studies, SD mice formed social avoidance memory and exhibited increased anxiety-like behavior. Importantly, subsequent MEM treatment (once a week for 4weeks) significantly reduced social avoidance behavior, suggesting that MEM-treated SD mice showed forgetting of social avoidance memory. Interestingly, MEM-treated SD mice showed comparable anxiety-like behavior with control mice that were not exposed to SD stress. Moreover, MEM-treated SD mice showed no reinstatement of social avoidance memory following single re-exposure to the aggressor. Our findings suggest that neurogenesis enhancer not only enhanced the forgetting of traumatic memory but also improved PTSD (anxiety)-like behavior.