塞沃兰通过抑制内部神经元上含有GluN2D的NMDA受体而起抗抑郁作用
Fei Guo1,2, Bing Zhang1, Fuyi Shen1
1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Department of Anesthesiology, Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
British journal of pharmacology
|May 23, 2024
概括
麻醉剂Sevoflurane通过向N-甲基-d-酸盐受体的GluN2D亚单元,表现出抗抑郁作用. 这种机制降低了内部神经元的活动,提供了潜在的新的抑郁症治疗方法.
科学领域:
- 神经科学是一个神经科学.
- 麻醉学 麻醉学
- 药理学 药理学是指药理学的学科.
背景情况:
- 塞沃弗兰是一种广泛使用的吸入麻醉剂,具有良好的安全性.
- 它的潜在抗抑郁药物特性和潜在机制在很大程度上仍未被探索.
- 这项研究调查了sevoflurane的抗抑郁作用和相关的神经生物学途径.
研究的目的:
- 为了阐明sevoflurane抗抑郁作用的作用机制.
- 为了确定sevoflurane是否针对中部前额皮层 (mPFC) 中的N-甲基-d-酸盐受体 (NMDARs).
- 评估GluN2D亚单元在赛沃兰抗抑郁作用中的作用.
主要方法:
- 在小鼠中进行行为测试,以评估抗抑郁药的效果.
- 在体外和体外全细胞补丁记录mPFC中的NMDARs.
- 电生理学在自由移动的小鼠中评估神经元活动.
- 使用GluN2D淘汰 (grin2d-/-) 鼠标来确认GluN2D.的作用.
主要成果:
- 重复的亚麻醉性塞沃弗卢兰剂量诱导持续抗抑郁作用长达两周.
- 塞沃兰选择性地抑制了含有GluN2C和GluN2D的NMDAR,降低了内部神经元的活动.
- 赛沃氨酸增加了金字塔神经元的发射,并减少了抑制电流,表明无抑制. 这些效应依赖于GluN2D.
结论:
- 塞沃兰的抗抑郁作用通过直接向GluN2D亚单元来调节.
- 这导致内部神经元活动降低和mPFC金字塔神经元的消抑制.
- 准GluN2D亚单元代表了抑郁症的有前途的治疗策略.
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