重新思考TRKB在抗抑郁药和迷幻药作用中的作用

IF 14.6 1区 医学 Q1 NEUROSCIENCES Trends in Neurosciences Pub Date : 2024-09-19 DOI:10.1016/j.tins.2024.08.011
Cecilia Anna Brunello, Cecilia Cannarozzo, Eero Castrén
{"title":"重新思考TRKB在抗抑郁药和迷幻药作用中的作用","authors":"Cecilia Anna Brunello, Cecilia Cannarozzo, Eero Castrén","doi":"10.1016/j.tins.2024.08.011","DOIUrl":null,"url":null,"abstract":"<p>Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.</p>","PeriodicalId":23325,"journal":{"name":"Trends in Neurosciences","volume":null,"pages":null},"PeriodicalIF":14.6000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Rethinking the role of TRKB in the action of antidepressants and psychedelics\",\"authors\":\"Cecilia Anna Brunello, Cecilia Cannarozzo, Eero Castrén\",\"doi\":\"10.1016/j.tins.2024.08.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.</p>\",\"PeriodicalId\":23325,\"journal\":{\"name\":\"Trends in Neurosciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":14.6000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Trends in Neurosciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.tins.2024.08.011\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Neurosciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tins.2024.08.011","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

摘要

抗抑郁药物能促进神经元的可塑性,而通过其受体神经元受体酪氨酸激酶2(NTRK2或TRKB)激活脑源性神经营养因子(BDNF)信号是这一过程的关键步骤之一。典型的慢效抗抑郁药、速效氯胺酮和迷幻化合物都具有这些机制,尽管每种药物的细胞靶点各不相同。在这一观点中,我们提出其中一些抗抑郁药可能直接与 TRKB 结合,并通过异体作用增强 BDNF 信号转导,以及其他可能的作用。含有副视蛋白的中间神经元中的TRKB激活会解除对大脑皮层网络的抑制,并重新激活类似幼年期的可塑性窗口。随后,异常网络的重新布线加上环境刺激,可能是其临床抗抑郁效果的基础。提出的端到端假说可能会刺激人们寻找新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Rethinking the role of TRKB in the action of antidepressants and psychedelics

Antidepressant drugs promote neuronal plasticity, and activation of brain-derived neurotrophic factor (BDNF) signaling through its receptor neuronal receptor tyrosine kinase 2 (NTRK2 or TRKB) is among the critical steps in this process. These mechanisms are shared by typical slow-acting antidepressants, fast-acting ketamine, and psychedelic compounds, although the cellular targets of each drug differ. In this opinion, we propose that some of these antidepressants may directly bind to TRKB and allosterically potentiate BDNF signaling, among other possible effects. TRKB activation in parvalbumin-containing interneurons disinhibits cortical networks and reactivates a juvenile-like plasticity window. Subsequent rewiring of aberrant networks, coupled with environmental stimuli, may underlie its clinical antidepressant effects. The end-to-end hypothesis proposed may stimulate the search for new treatment strategies.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Trends in Neurosciences
Trends in Neurosciences 医学-神经科学
CiteScore
26.50
自引率
1.30%
发文量
123
审稿时长
6-12 weeks
期刊介绍: For over four decades, Trends in Neurosciences (TINS) has been a prominent source of inspiring reviews and commentaries across all disciplines of neuroscience. TINS is a monthly, peer-reviewed journal, and its articles are curated by the Editor and authored by leading researchers in their respective fields. The journal communicates exciting advances in brain research, serves as a voice for the global neuroscience community, and highlights the contribution of neuroscientific research to medicine and society.
期刊最新文献
The claustrum and synchronized brain states. Dopaminergic circuits controlling threat and safety learning. Principles of intensive human neuroimaging. Retinal ganglion cell circuits and glial interactions in humans and mice. CAMs in command: aging brain macrophages fine-tune stroke immune responses.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1