齿状回未成熟颗粒神经元在氯胺酮快速抗抑郁中作用的最新研究进展

doi:10.12300/j.issn.1674-5817.2022.146

实验动物与比较医学 ›› 2022, Vol. 42 ›› Issue (5): 377-383.DOI: 10.12300/j.issn.1674-5817.2022.146

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齿状回未成熟颗粒神经元在氯胺酮快速抗抑郁中作用的最新研究进展

魏盛()(), 耿希文(), 赵峰, 李自发, 张浩, 胡明会

山东中医药大学实验中心, 济南 250355

收稿日期:2022-09-13 修回日期:2022-10-06 出版日期:2022-10-25 发布日期:2022-10-25
作者简介:魏盛（1980—），男，教授，研究方向：中医情志病证的脑环路基础及中医药干预机制。E-mail：weisheng@sdutcm.edu.cn。ORCID：0000-0002-1326-4625
耿希文（1990—），女，副教授，研究方向：情志病证神经环路及中药干预机制。E-mail：xwgeng@sdutcm.edu.cn。ORCID：0000-0002-6112-7385
基金资助:
国家自然科学基金资助项目“内侧前额叶皮质GABA能中间神经元介导的去抑制在中药舒郁胶囊干预抑郁症肝气郁结证中的作用”(82274383);“从中枢PAG区对ALLO波动敏感性探讨中药舒郁胶囊对PMDD肝气郁证干预机制”(81974553);山东省自然科学基金重大基础研究项目“抑郁症、焦虑症不同病证神经环路解析及其中医药干预机制研究”(ZR2020ZD17);“山东中医药大学中医药与脑科学青年科研创新团队”(22202101)

Recent Research Progress of the Mechanism of Adult-born Immature Granule Neurons Underlying Rapid Antidepressant Effect of Ketamine

Sheng WEI()(), Xiwen GENG(), Feng ZHAO, Zifa LI, Hao ZHANG, Minghui HU

Experiment Center of Shandong University of Traditional Chinese Medicine, Jinan 250355, China

Received:2022-09-13 Revised:2022-10-06 Published:2022-10-25 Online:2022-10-25
Contact: WEI Sheng (ORCID:0000-0002-1326-4625), E-mail: weisheng@sdutcm.edu.cn

摘要/Abstract

摘要：

重度抑郁症已经成为困扰人类健康的重大疾病，传统的抗抑郁药物由于起效慢、不良反应大等缺陷，在临床应用中存在很大局限性。近年来，氯胺酮数小时起效的快速抗抑郁作用备受人们关注，但其神经机制不明了，制约了该药物的临床应用。2022年5月Nature Communications杂志发表Rawat等的研究报告，证实了小鼠海马齿状回中未成熟颗粒神经元的急性激活在氯胺酮的快速抗抑郁作用中扮演着关键角色。本文对这一研究做文献分析，并对后续相关工作进行展望。

关键词: 重度抑郁症, 氯胺酮, 快速抗抑郁, 齿状回, 未成熟颗粒神经元

Abstract:

Major depressive disorder is a serious disease that impacts human health worldwide. Traditional antidepressant medications are limited by the delayed onset of therapeutic effects and the unacceptable side effects. Recently, the rapid antidepressant effect of ketamine, which decreases depressive symptoms within hours, has been a very attractive finding in the field, but the underlying mechanisms mediating this rapid response remain unclear. Besides, the clinical application of ketamine still carries risks, such as addiction and deleterious side effects. In May 2022, Rawat et al. reported that the acute activation of adult-born immature granule neurons (ABINs) in the dentate gyrus played a key role in the rapid antidepressant effects of ketamine. This commentary reviews the important findings of this research and looks forward to the future work.

Key words: Major depressive disorder, Ketamine, Rapid antidepressant effect, Dentate gyrus, Adult-born immature granule neurons

中图分类号:

R-338

魏盛,耿希文,赵峰,等. 齿状回未成熟颗粒神经元在氯胺酮快速抗抑郁中作用的最新研究进展[J]. 实验动物与比较医学, 2022, 42(5): 377-383. DOI: 10.12300/j.issn.1674-5817.2022.146.

Sheng WEI,Xiwen GENG,Feng ZHAO,et al. Recent Research Progress of the Mechanism of Adult-born Immature Granule Neurons Underlying Rapid Antidepressant Effect of Ketamine[J]. Laboratory Animal and Comparative Medicine, 2022, 42(5): 377-383. DOI: 10.12300/j.issn.1674-5817.2022.146.

图/表 3

图1 氯胺酮通过阻断NMDA受体抑制外侧僵核簇状放电以发挥快速抗抑郁效应注：笔者根据文献［4-5］内容绘制而成。

Figure1 Ketamine blocks the function of NMDA receptors, decreases neuronal bursting, and rescues depression-like phenotypesNote： This figure is based on published data ［4-5］, which was drawn by the authors of this article.

图2 Rawat等（2022年）的实验设计技术路线解读示意图注：笔者根据参考文献［13］内容整理。

Figure 2 Schematic diagram of the experimental design of Rawat et al. (2022)Note： This diagram was generated based on published data ［13］， which was drawn by authors of this article.

图3 氯胺酮快速抗抑郁的神经环路机制示意图注：笔者根据文献［18，22］内容绘制而成。BLA为基底外侧杏仁核；BNST为终纹床核；DRN为中缝背核；LHb为外侧僵核；MDT为丘脑背中核；mPFC为内侧前额叶皮质；RMTg为吻内侧被盖核；vHPC为背侧海马；VTA为中脑腹侧被盖区。

Figure 3 Neural circuits involved in the antidepressant actions of ketamineNote： This figure is based on published data ［18， 22］， which was drawn by authors of this article. BLA， basolateral amygdala； BNST， bed nucleus of the stria terminalis； DRN， dorsal raphe nucleus； LHb， lateral habenula； MDT， mediodorsal nucleus of the thalamus； mPFC， medial prefrontal cortex； RMTg， rostromedial tegmental nucleus； vHPC， ventral hippocampus； VTA， ventral tegmental area.

参考文献 23

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齿状回未成熟颗粒神经元在氯胺酮快速抗抑郁中作用的最新研究进展

Recent Research Progress of the Mechanism of Adult-born Immature Granule Neurons Underlying Rapid Antidepressant Effect of Ketamine

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