Transient suppression of progenitor cell proliferation through NMDA receptors in hippocampal dentate gyrus of mice with traumatic stress experience
Transient suppression of progenitor cell proliferation through NMDA receptors in hippocampal dentate gyrus of mice with traumatic stress experience
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DOI：
10.1111/j.1471-4159.2008.05253.x
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Yoneda, Yukio
中科院分区：
文献类型：
--
作者：
Tamaki, Keisuke;Yamada, Kiyofumi;Yoneda, Yukio
创伤后应激障碍是一种长期持续的精神疾病，是在经历严重致命应激的创伤后导致海马萎缩的结果。在 WIRS 后 1-128 天进行测定时，先前接受带有节拍器音调的水浸抑制应激 (WIRS) 的小鼠在恐惧条件反射测试中的冻结行为增加了五倍多，而这些小鼠在强迫游泳测试中表现出不动时间增加，自发运动增加。之前的 WIRS 经验导致海马齿状回增殖细胞中随后的 5-溴-2'-脱氧尿苷 (BrdU) 掺入暂时减少。每天注射三环类抗抑郁药丙咪嗪和选择性血清素再摄取抑制剂氟伏沙明可以显着预防这些行为和神经化学改变。此外，WIRS 显着减少了持有 BrdU 的细胞数量，而不影响 28 天后向星形胶质细胞和神经元谱系的分化比例。预先施用 NMDA 受体拮抗剂可显着阻止 WIRS 引起的上述变化。这些结果表明，NMDA 受体可能通过短暂抑制小鼠海马齿状回神经祖细胞增殖，在与创伤后应激障碍相关的各种精神症状危机的机制中发挥作用。
Post-traumatic stress disorder is a long-lasting psychiatric disease after the traumatic experience of severe fatal stress with the consequence of hippocampal atrophy. Freezing behaviors were more than quintupled on the fear-conditioning test in mice previously subjected to water immersion restrain stress (WIRS) with metronome tones when determined 1-128 days after WIRS, while these mice exhibited the increased immobility time on the forced swimming test with the increased spontaneous locomotion. Prior experience of WIRS led to a transient decrease in subsequent 5-bromo-2'-deoxyuridine (BrdU) incorporation into proliferating cells in the hippocampal dentate gyrus. These behavioral and neurochemical alterations were significantly prevented by the daily injection of the tricyclic antidepressant imipramine and the selective serotonin reuptake inhibitor fluvoxamine, respectively. Moreover, WIRS significantly decreased the number of cells holding BrdU without affecting the differentiation ratio to astroglial and neuronal lineages 28 days later. Prior administration of an NMDA receptor antagonist significantly prevented the aforementioned changes by WIRS. These results suggest that NMDA receptors may play a role in mechanisms underlying the crisis of a variety of psychiatric symptoms relevant to post-traumatic stress disorder through transient suppression of neural progenitor cell proliferation in the murine hippocampal dentate gyrus.