Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice
文献类型：期刊论文
| 作者 | Tillmon, Haven9; Soteros, Breeanne M.9; Shen, Liang8; Cong, Qifei6,7,8; Wollet, Mackenna5; General, Julianne9; Chin, Hanna4; Lee, John Beichen3; Carreno, Flavia R.9; Morilak, David A.2,9 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2024-11-12 |
| 卷号 | 15期号:1页码:17 |
| DOI | 10.1038/s41467-024-54007-5 |
| 英文摘要 | Spatially heterogeneous synapse loss is a characteristic of many psychiatric and neurological disorders, but the underlying mechanisms are unclear. Here, we show that spatially-restricted complement activation mediates stress-induced heterogeneous microglia activation and synapse loss localized to the upper layers of the medial prefrontal cortex (mPFC) in male mice. Single cell RNA sequencing also reveals a stress-associated microglia state marked by high expression of the apolipoprotein E gene (Apoehigh) localized to the upper layers of the mPFC. Mice lacking complement component C3 are protected from stress-induced layer-specific synapse loss, and the Apoehigh microglia population is markedly reduced in the mPFC of these mice. Furthermore, C3 knockout mice are also resilient to stress-induced anhedonia and working memory behavioral deficits. Our findings suggest that region-specific complement and microglia activation can contribute to the disease-specific spatially restricted patterns of synapse loss and clinical symptoms found in many brain diseases. Synapse loss is central to the pathogenesis of stress-related disorders. Here, the authors show that targeted synapse removal by microglia and complement during stress contributes to the effects of stress on behavior. |
| WOS关键词 | DENDRITIC SPINE DENSITY ; CORTICAL PYRAMIDAL NEURONS ; GRAY-MATTER VOLUME ; ALZHEIMERS-DISEASE ; SALIVARY CORTISOL ; SENILE PLAQUES ; SCHIZOPHRENIA ; CONNECTIVITY ; DEPRESSION ; REDUCTIONS |
| 资助项目 | U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)[R01NS112389] ; National Institute of Neurological Disorders and Stroke (NINDS) grant[R01MH053851] ; National Institute of Mental Health (NIMH)[R01DC018797] ; National Institute of Mental Health (NIMH)[R01DC019371] ; National Institute on Deafness and other Communication Disorders (NIDCD)[R21MH113899] ; NIMH[P30CA54174] ; NCI[P30CA054174] ; NCI grant[RP210126] ; Cancer Prevention and Research Institute of Texas (CPRIT)[S10OD030432] ; National Institutes of Health (NIH) Shared Instrument grant[S10OD030311] ; NIH Shared Instrument grant[RP220662] ; CPRIT core facility award[32200778] ; Natural Science Foundation of China[BK20220494] ; Natural Science Foundation of Jiangsu Province grant[SKY2022107] ; Suzhou Medical and Health Technology Innovation Project[ND2022A04] ; Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow University[SKLDR-2023-KF-05] ; State Key Laboratory of Drug Research grant[KYCX24_3335] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province grant |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001354231300016 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/316230]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Sia, Gek Ming |
| 作者单位 | 1.Univ Michigan, Kresge Hearing Res Inst, Ann Arbor, MI 48109 USA 2.South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA 3.Univ Texas Hlth San Antonio, Long Sch Med, San Antonio, TX 78229 USA 4.Univ Rochester, Rochester, NY 14627 USA 5.Univ Texas Hlth San Antonio, Dept Cellular & Integrat Physiol, San Antonio, TX 78229 USA 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Soochow Univ, Affiliated Hosp 2, Clin Res Ctr Neurol Dis, Dept Nephrol, Suzhou 215004, Peoples R China 8.Soochow Univ, Inst Neurosci, Suzhou 215123, Peoples R China 9.Univ Texas Hlth San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA |
| 推荐引用方式 GB/T 7714 | Tillmon, Haven,Soteros, Breeanne M.,Shen, Liang,et al. Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice[J]. NATURE COMMUNICATIONS,2024,15(1):17. |
| APA | Tillmon, Haven.,Soteros, Breeanne M..,Shen, Liang.,Cong, Qifei.,Wollet, Mackenna.,...&Sia, Gek Ming.(2024).Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice.NATURE COMMUNICATIONS,15(1),17. |
| MLA | Tillmon, Haven,et al."Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice".NATURE COMMUNICATIONS 15.1(2024):17. |
入库方式： OAI收割
来源：上海药物研究所
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