• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

星形胶质细胞在抑郁症中的作用及其通过靶向星形胶质细胞神经递质释放的预防和治疗。

The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release.

机构信息

Center for Bioinformatics and Integrative Biology, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, Chile.

Laboratorio de Neurobiología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad Andres Bello, Santiago 8370146, Chile.

出版信息

Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2307953121. doi: 10.1073/pnas.2307953121. Epub 2024 Nov 4.

DOI:10.1073/pnas.2307953121
PMID:39495924
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11572930/
Abstract

The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.

摘要

腹侧海马体（vHipp）星形胶质细胞神经递质传递在抑郁症中的作用是使用慢性束缚应激（CRS）和慢性不可预测轻度应激（CUMS）啮齿动物模型研究的。CRS 增加了 vHipp 中的 Cx43 半通道活性和细胞外谷氨酸水平，并且在 CRS 期间阻断星形胶质细胞 Cx43 半通道依赖性神经递质传递可防止抑郁和谷氨酸积累的发展。此外，急性阻断 Cx43 半通道在先前接受 CRS 或 CUMS 的大鼠中诱导抗抑郁作用。谷氨酸和 D-丝氨酸共注射可预防这种抗抑郁作用。此外，Cx43 半通道阻断以谷氨酸和 D-丝氨酸依赖的方式降低 vHipp 切片中的突触后 NMDA 受体电流。值得注意的是，慢性微量灌注谷氨酸和 D-丝氨酸、L-丝氨酸或 NMDA 受体激动剂 NMDA 到 vHipp 中会在未应激的大鼠中引起类似抑郁的症状。我们还鉴定出一种小分子 cacotheline，它可阻断 Cx43 半通道，其全身给药可迅速诱导抗抑郁作用，防止应激引起的 vHipp 中星形胶质细胞 Cx43 半通道活性和细胞外谷氨酸增加，而没有镇静或运动副作用。总之，慢性应激会增加 vHipp 中星形胶质细胞 Cx43 半通道依赖性谷氨酸和 D-/L-丝氨酸的释放，过度激活突触后 NMDA 受体并引发类似抑郁的症状。这项研究强调了星形胶质细胞神经递质释放在慢性应激诱导的抑郁症中的关键作用，并表明它可以作为预防和治疗抑郁症的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/01f675501daa/pnas.2307953121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/cddc91fbfacf/pnas.2307953121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/c93ffe673ee7/pnas.2307953121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/83527b4015ed/pnas.2307953121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/a4bdc9ea7ff2/pnas.2307953121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/01f675501daa/pnas.2307953121fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/cddc91fbfacf/pnas.2307953121fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/c93ffe673ee7/pnas.2307953121fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/83527b4015ed/pnas.2307953121fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/a4bdc9ea7ff2/pnas.2307953121fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed38/11572930/01f675501daa/pnas.2307953121fig05.jpg

相似文献

1
The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release.星形胶质细胞在抑郁症中的作用及其通过靶向星形胶质细胞神经递质释放的预防和治疗。
Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2307953121. doi: 10.1073/pnas.2307953121. Epub 2024 Nov 4.
2
Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala.缝隙连接蛋白 43 半通道释放的星形胶质细胞神经递质调节外侧杏仁核中 NMDAR 依赖的传递和短期恐惧记忆。
FASEB J. 2022 Feb;36(2):e22134. doi: 10.1096/fj.202100798RR.
3
Contribution of Astroglial Cx43 Hemichannels to the Modulation of Glutamatergic Currents by D-Serine in the Mouse Prefrontal Cortex.星形胶质细胞Cx43半通道对D-丝氨酸调节小鼠前额叶皮质谷氨酸能电流的作用
J Neurosci. 2017 Sep 13;37(37):9064-9075. doi: 10.1523/JNEUROSCI.2204-16.2017. Epub 2017 Aug 11.
4
Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.星形胶质细胞缝隙连接蛋白 43 半通道释放神经递质对于基底外侧杏仁核的恐惧记忆巩固是必要的。
FASEB J. 2012 Sep;26(9):3649-57. doi: 10.1096/fj.11-198416. Epub 2012 Jun 4.
5
GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels.GABA 能神经元通过缝隙连接蛋白 43 调控星形胶质细胞的胞吐作用。
Int J Mol Sci. 2022 Nov 7;23(21):13625. doi: 10.3390/ijms232113625.
6
Distinct Effects of Escitalopram and Vortioxetine on Astroglial L-Glutamate Release Associated with Connexin43.依他普仑和文拉法辛对缝隙连接蛋白 43 相关星形胶质细胞 L-谷氨酸释放的不同影响。
Int J Mol Sci. 2021 Sep 16;22(18):10013. doi: 10.3390/ijms221810013.
7
Effects of Carbamazepine, Lacosamide and Zonisamide on Gliotransmitter Release Associated with Activated Astroglial Hemichannels.卡马西平、拉科酰胺和唑尼沙胺对与活化星形胶质细胞半通道相关的神经胶质递质释放的影响。
Pharmaceuticals (Basel). 2020 Jun 5;13(6):117. doi: 10.3390/ph13060117.
8
Ifenprodil rapidly ameliorates depressive-like behaviors, activates mTOR signaling and modulates proinflammatory cytokines in the hippocampus of CUMS rats.依酚氯胺可迅速改善抑郁样行为，激活 mTOR 信号通路，并调节 CUMS 大鼠海马中的促炎细胞因子。
Psychopharmacology (Berl). 2020 May;237(5):1421-1433. doi: 10.1007/s00213-020-05469-0. Epub 2020 Mar 4.
9
Brivaracetam and Levetiracetam Suppress Astroglial L-Glutamate Release through Hemichannel via Inhibition of Synaptic Vesicle Protein.布瓦西坦和左乙拉西坦通过抑制突触囊泡蛋白经由缝隙连接抑制星形胶质细胞 L-谷氨酸释放。
Int J Mol Sci. 2022 Apr 19;23(9):4473. doi: 10.3390/ijms23094473.
10
Ultrafine carbon black induces glutamate and ATP release by activating connexin and pannexin hemichannels in cultured astrocytes.超细碳黑通过激活培养星形胶质细胞中的连接蛋白和缝隙连接蛋白半通道诱导谷氨酸和 ATP 释放。
Toxicology. 2014 Sep 2;323:32-41. doi: 10.1016/j.tox.2014.06.005. Epub 2014 Jun 13.

引用本文的文献

1
Connexin43 and Its Regulation of Astrocyte Gap Junction Function: Influencing Depression Progression by Mediating Electrical and Chemical Signals.连接蛋白43及其对星形胶质细胞缝隙连接功能的调节：通过介导电信号和化学信号影响抑郁症进展
CNS Neurosci Ther. 2025 Sep;31(9):e70600. doi: 10.1111/cns.70600.
2
When the Stars Misfire: Astrocytic Dysfunctions in Major Depressive Disorder.当星星失去火力：重度抑郁症中的星形胶质细胞功能障碍
Neurochem Res. 2025 Jul 12;50(4):231. doi: 10.1007/s11064-025-04483-y.
3
Untargeted metabolomics revealed that quercetin improves rat renal metabolic disorders induced by chronic unpredictable mild stress.

本文引用的文献

1
Acute activation of hemichannels by ethanol leads to Ca-dependent gliotransmitter release in astrocytes.乙醇对半通道的急性激活会导致星形胶质细胞中依赖钙的神经胶质递质释放。
Front Cell Dev Biol. 2024 Jun 21;12:1422978. doi: 10.3389/fcell.2024.1422978. eCollection 2024.
2
Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.重复皮下注射氯胺酮治疗难治性抑郁症 4 周的疗效和安全性（KADS 研究）：随机双盲活性对照试验。
Br J Psychiatry. 2023 Dec;223(6):533-541. doi: 10.1192/bjp.2023.79.
3
The connexin hemichannel inhibitor D4 produces rapid antidepressant-like effects in mice.
非靶向代谢组学研究表明，槲皮素可改善慢性不可预测轻度应激诱导的大鼠肾脏代谢紊乱。
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 25. doi: 10.1007/s00210-025-04186-9.
4
Research progress of connexins in epileptogensis.连接蛋白在癫痫发生中的研究进展
Acta Epileptol. 2025 Mar 15;7(1):14. doi: 10.1186/s42494-025-00203-9.
5
Benchmarking macaque brain gene expression for horizontal and vertical translation.对猕猴大脑基因表达进行水平和垂直翻译的基准测试。
Sci Adv. 2025 Feb 28;11(9):eads6967. doi: 10.1126/sciadv.ads6967.
连接蛋白半通道抑制剂 D4 可迅速在小鼠体内产生抗抑郁样作用。
J Neuroinflammation. 2023 Aug 20;20(1):191. doi: 10.1186/s12974-023-02873-z.
4
Brain-wide changes in excitation-inhibition balance of major depressive disorder: a systematic review of topographic patterns of GABA- and glutamatergic alterations.重度抑郁症脑内兴奋-抑制平衡的全脑变化：γ-氨基丁酸和谷氨酸能改变的地形学模式的系统评价
Mol Psychiatry. 2023 Aug;28(8):3257-3266. doi: 10.1038/s41380-023-02193-x. Epub 2023 Jul 26.
5
Caspase-1 affects chronic restraint stress-induced depression-like behaviors by modifying GABAergic dysfunction in the hippocampus.Caspase-1 通过调节海马 GABA 能功能障碍影响慢性束缚应激诱导的抑郁样行为。
Transl Psychiatry. 2023 Jun 27;13(1):229. doi: 10.1038/s41398-023-02527-x.
6
Astrocyte Calcium Signaling Shifts the Polarity of Presynaptic Plasticity.星形胶质细胞钙信号改变了突触前可塑性的极性。
Neuroscience. 2023 Aug 10;525:38-46. doi: 10.1016/j.neuroscience.2023.05.032. Epub 2023 Jun 7.
7
Astroglial Connexin 43 Regulates Synaptic Vesicle Release at Hippocampal Synapses.星形胶质细胞连接蛋白 43 调节海马突触的突触囊泡释放。
Cells. 2023 Apr 11;12(8):1133. doi: 10.3390/cells12081133.
8
Dysfunction of Glutamatergic Synaptic Transmission in Depression: Focus on AMPA Receptor Trafficking.抑郁症中谷氨酸能突触传递功能障碍：聚焦于AMPA受体转运
Biol Psychiatry Glob Open Sci. 2022 Mar 8;3(2):187-196. doi: 10.1016/j.bpsgos.2022.02.007. eCollection 2023 Apr.
9
Connexin 43: An Interface Connecting Neuroinflammation to Depression.间隙连接蛋白 43：连接神经炎症与抑郁症的纽带
Molecules. 2023 Feb 15;28(4):1820. doi: 10.3390/molecules28041820.
10
Role of Connexin 43 phosphorylation on Serine-368 by PKC in cardiac function and disease.蛋白激酶C使连接蛋白43的丝氨酸-368位点磷酸化在心脏功能和疾病中的作用
Front Cardiovasc Med. 2023 Jan 12;9:1080131. doi: 10.3389/fcvm.2022.1080131. eCollection 2022.