用迷幻药预防痴呆症?迷幻药在改变重度抑郁症和神经退行性疾病相关机制方面的潜在作用

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacology & Therapeutics Pub Date : 2024-04-06 DOI:10.1016/j.pharmthera.2024.108641
Zarah R. Haniff , Mariia Bocharova , Tim Mantingh , James J. Rucker , Latha Velayudhan , David M. Taylor , Allan H. Young , Dag Aarsland , Anthony C. Vernon , Sandrine Thuret
{"title":"用迷幻药预防痴呆症?迷幻药在改变重度抑郁症和神经退行性疾病相关机制方面的潜在作用","authors":"Zarah R. Haniff ,&nbsp;Mariia Bocharova ,&nbsp;Tim Mantingh ,&nbsp;James J. Rucker ,&nbsp;Latha Velayudhan ,&nbsp;David M. Taylor ,&nbsp;Allan H. Young ,&nbsp;Dag Aarsland ,&nbsp;Anthony C. Vernon ,&nbsp;Sandrine Thuret","doi":"10.1016/j.pharmthera.2024.108641","DOIUrl":null,"url":null,"abstract":"<div><p>Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases.</p><p>Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":null,"pages":null},"PeriodicalIF":12.0000,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163725824000615/pdfft?md5=862308f7cd3837dabdd6124f68df8bf8&pid=1-s2.0-S0163725824000615-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases\",\"authors\":\"Zarah R. Haniff ,&nbsp;Mariia Bocharova ,&nbsp;Tim Mantingh ,&nbsp;James J. Rucker ,&nbsp;Latha Velayudhan ,&nbsp;David M. Taylor ,&nbsp;Allan H. Young ,&nbsp;Dag Aarsland ,&nbsp;Anthony C. Vernon ,&nbsp;Sandrine Thuret\",\"doi\":\"10.1016/j.pharmthera.2024.108641\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases.</p><p>Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.</p></div>\",\"PeriodicalId\":402,\"journal\":{\"name\":\"Pharmacology & Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.0000,\"publicationDate\":\"2024-04-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0163725824000615/pdfft?md5=862308f7cd3837dabdd6124f68df8bf8&pid=1-s2.0-S0163725824000615-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0163725824000615\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163725824000615","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

摘要

重度抑郁是继发痴呆症的既定风险因素,晚年抑郁也可能是痴呆症的前兆状态。考虑到目前临床开发痴呆症疾病调节疗法所面临的挑战,研究重点正转向预防和改变风险因素,以改变神经退行性疾病的发展轨迹。了解情感症状和认知能力下降的机理共性可能会发现一些生物标志物,有助于在疾病的临床前阶段及早识别那些有可能发展成痴呆症的人,从而进行及时干预。成人海马神经发生(AHN)是一种描述齿状回终生诞生新神经元的现象,它与空间学习、记忆和情绪调节有关。小胶质细胞是中枢神经系统中的先天性免疫系统巨噬细胞,它通过多种机制仔细调节 AHN。AHN 的破坏与痴呆症和重度抑郁症有关,而小胶质细胞病变则是多种神经退行性疾病的标志。在这种情况下,迷幻药作为一种具有速效抗抑郁特性的血清素能激动剂,有可能改善与重度抑郁症和神经退行性疾病相关的交叉病理生理过程。在这篇叙述性综述中,我们将重点关注迷幻药对成人海马神经发生和小胶质细胞形态与功能影响的证据基础;这可能表明迷幻药具有调节多种作用机制的潜力,并可能对改变高危人群从重度抑郁症发展为痴呆症的过程产生影响。
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
Psilocybin for dementia prevention? The potential role of psilocybin to alter mechanisms associated with major depression and neurodegenerative diseases

Major depression is an established risk factor for subsequent dementia, and depression in late life may also represent a prodromal state of dementia. Considering current challenges in the clinical development of disease modifying therapies for dementia, the focus of research is shifting towards prevention and modification of risk factors to alter the neurodegenerative disease trajectory. Understanding mechanistic commonalities underlying affective symptoms and cognitive decline may reveal biomarkers to aid early identification of those at risk of progressing to dementia during the preclinical phase of disease, thus allowing for timely intervention. Adult hippocampal neurogenesis (AHN) is a phenomenon that describes the birth of new neurons in the dentate gyrus throughout life and it is associated with spatial learning, memory and mood regulation. Microglia are innate immune system macrophages in the central nervous system that carefully regulate AHN via multiple mechanisms. Disruption in AHN is associated with both dementia and major depression and microgliosis is a hallmark of several neurodegenerative diseases.

Emerging evidence suggests that psychedelics promote neuroplasticity, including neurogenesis, and may also be immunomodulatory. In this context, psilocybin, a serotonergic agonist with rapid-acting antidepressant properties has the potential to ameliorate intersecting pathophysiological processes relevant for both major depression and neurodegenerative diseases. In this narrative review, we focus on the evidence base for the effects of psilocybin on adult hippocampal neurogenesis and microglial form and function; which may suggest that psilocybin has the potential to modulate multiple mechanisms of action, and may have implications in altering the progression from major depression to dementia in those at risk.

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
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
期刊介绍: Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.
期刊最新文献
Lipoprotection in cardiovascular diseases. Nutraceuticals target androgen receptor-splice variants (AR-SV) to manage castration resistant prostate cancer (CRPC). Editorial Board The voltage sensitivity of G-protein coupled receptors: Unraveling molecular mechanisms and physiological implications. Oxytocin in neurodevelopmental disorders: Autism spectrum disorder and Prader-Willi syndrome.
×
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