• 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

自噬性神经干细胞死亡介导慢性应激导致的成年海马神经发生减少和认知缺陷。

Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits.

机构信息

Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea.

BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon, Republic of Korea.

出版信息

Autophagy. 2020 Mar;16(3):512-530. doi: 10.1080/15548627.2019.1630222. Epub 2019 Jun 24.

DOI:10.1080/15548627.2019.1630222
PMID:31234698
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6999625/
Abstract

Macroautophagy/autophagy is generally regarded as a cytoprotective mechanism, and it remains a matter of controversy whether autophagy can cause cell death in mammals. Here, we show that chronic restraint stress suppresses adult hippocampal neurogenesis in mice by inducing autophagic cell death (ACD) of hippocampal neural stem cells (NSCs). We generated NSC-specific, inducible conditional knockout mice and found that they had an intact number of NSCs and neurogenesis level under chronic restraint stress and were resilient to stress- or corticosterone-induced cognitive and mood deficits. Corticosterone treatment of adult hippocampal NSC cultures induced ACD via SGK3 (serum/glucocorticoid regulated kinase 3) without signs of apoptosis. Our results demonstrate that ACD is biologically important in a mammalian system and would be an attractive target for therapeutic intervention for psychological stress-induced disorders.: AAV: adeno-associated virus; ACD: autophagic cell death; ACTB: actin, beta; Atg: autophagy-related; ASCL1/MASH1: achaete-scute family bHLH transcription factor 1; BafA: bafilomycin A; BrdU: Bromodeoxyuridine/5-bromo-2'-deoxyuridine; CASP3: caspase 3; cKO: conditional knockout; CLEM: correlative light and electron microscopy; CORT: corticosterone; CRS: chronic restraint stress; DAB: 3,3'-diaminobenzidine; DCX: doublecortin; DG: dentate gyrus; GC: glucocorticoid; GFAP: glial fibrillary acidic protein; HCN: hippocampal neural stem; i.p.: intraperitoneal; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MKI67/Ki67: antigen identified by monoclonal antibody Ki 67; MWM: Morris water maze; Nec-1: necrostatin-1; NES: nestin; NR3C1/GR: nuclear receptor subfamily 3, group C, member 1; NSC: neural stem cell; PCD: programmed cell death; PFA: paraformaldehyde; PX: Phox homology; PtdIns3P: phosphatidylinositol-3-phosphate; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; SGK: serum/glucocorticoid-regulated kinases; SGZ: subgranular zone; SOX2: SRY (sex determining region Y)-box 2; SQSTM1: sequestosome 1; STS: staurosporine; TAM: tamoxifen; Ulk1: unc-51 like kinase 1; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VIM: vimentin; WT: wild type; ZFYVE1: zinc finger, FYVE domain containing 1; Z-VAD/Z-VAD-FMK: pan-caspase inhibitor.

摘要

自噬通常被认为是一种细胞保护机制，但自噬是否会导致哺乳动物细胞死亡仍然存在争议。在这里，我们表明慢性束缚应激通过诱导海马神经干细胞（NSC）的自噬细胞死亡（ACD）来抑制小鼠成年海马神经发生。我们生成了 NSC 特异性、诱导型条件性敲除小鼠，并发现它们在慢性束缚应激下具有完整的 NSC 数量和神经发生水平，并且对应激或皮质酮诱导的认知和情绪缺陷具有弹性。皮质酮处理成年海马 NSC 培养物通过 SGK3（血清/糖皮质激素调节激酶 3）诱导 ACD，而没有凋亡的迹象。我们的结果表明，ACD 在哺乳动物系统中具有重要的生物学意义，并且可能成为治疗心理应激诱导障碍的有吸引力的靶点。AAV：腺相关病毒；ACD：自噬细胞死亡；ACTB：肌动蛋白，β；Atg：自噬相关；ASCL1/MASH1：achaete-scute 家族 bHLH 转录因子 1；BafA：巴弗霉素 A；BrdU：溴脱氧尿苷/5-溴-2'-脱氧尿苷；CASP3：半胱天冬酶 3；cKO：条件性敲除；CLEM：相关光镜和电子显微镜；CORT：皮质酮；CRS：慢性束缚应激；DAB：3,3'-二氨基联苯胺；DCX：双皮质素；DG：齿状回；GC：糖皮质激素；GFAP：胶质纤维酸性蛋白；HCN：海马神经干细胞；i.p.：腹腔内；MAP1LC3B：微管相关蛋白 1 轻链 3β；MKI67/Ki67：由单克隆抗体 Ki 67 识别的抗原；MWM：莫里斯水迷宫；Nec-1：necrostatin-1；PX：Phox 同源物；PtdIns3P：磷脂酰肌醇-3-磷酸；RBFOX3/NeuN：RNA 结合蛋白，fox-1 同源物（C. elegans）3；SGK：血清/糖皮质激素调节激酶；SGZ：颗粒下层区；SOX2：SRY（性别决定区 Y）-盒 2；SQSTM1：自噬体相关蛋白 1；STS：staurosporine；TAM：他莫昔芬；Ulk1：unc-51 样激酶 1；TUNEL：末端脱氧核苷酸转移酶 dUTP 缺口末端标记；VIM：波形蛋白；WT：野生型；ZFYVE1：锌指、FYVE 结构域包含 1；Z-VAD/Z-VAD-FMK：pan-caspase 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/de905b21c9c1/kaup-16-03-1630222-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/71f4f52e687f/kaup-16-03-1630222-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/7b2be5ebf793/kaup-16-03-1630222-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/4e755ba29b40/kaup-16-03-1630222-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/19ded7afa30f/kaup-16-03-1630222-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/125af6d91938/kaup-16-03-1630222-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/21af917f1b90/kaup-16-03-1630222-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/647f4f994dec/kaup-16-03-1630222-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/5c7152d9f1a0/kaup-16-03-1630222-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/2cb2dc8905de/kaup-16-03-1630222-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/de905b21c9c1/kaup-16-03-1630222-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/71f4f52e687f/kaup-16-03-1630222-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/7b2be5ebf793/kaup-16-03-1630222-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/4e755ba29b40/kaup-16-03-1630222-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/19ded7afa30f/kaup-16-03-1630222-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/125af6d91938/kaup-16-03-1630222-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/21af917f1b90/kaup-16-03-1630222-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/647f4f994dec/kaup-16-03-1630222-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/5c7152d9f1a0/kaup-16-03-1630222-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/2cb2dc8905de/kaup-16-03-1630222-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df6/6999625/de905b21c9c1/kaup-16-03-1630222-g010.jpg

相似文献

1
Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits.自噬性神经干细胞死亡介导慢性应激导致的成年海马神经发生减少和认知缺陷。
Autophagy. 2020 Mar;16(3):512-530. doi: 10.1080/15548627.2019.1630222. Epub 2019 Jun 24.
2
ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease.自噬相关蛋白 5（ATG5）在小胶质细胞中控制阿尔茨海默病中的海马神经发生。
Autophagy. 2024 Apr;20(4):847-862. doi: 10.1080/15548627.2023.2277634. Epub 2023 Nov 10.
3
CASP9 (caspase 9) is essential for autophagosome maturation through regulation of mitochondrial homeostasis.CASP9（半胱氨酸天冬氨酸蛋白酶 9）通过调节线粒体稳态对于自噬体成熟是必不可少的。
Autophagy. 2020 Sep;16(9):1598-1617. doi: 10.1080/15548627.2019.1695398. Epub 2019 Dec 10.
4
Enhanced autophagy in knockin mice counteracts aging-related neural stem cell exhaustion and dysfunction.基因敲入小鼠中的自噬增强可抵抗与衰老相关的神经干细胞耗竭和功能障碍。
Autophagy. 2022 Feb;18(2):409-422. doi: 10.1080/15548627.2021.1936358. Epub 2021 Jun 8.
5
Chronic unpredictable stress induces autophagic death of adult hippocampal neural stem cells.慢性不可预测应激诱导成年海马神经干细胞自噬性死亡。
Mol Brain. 2024 Jun 3;17(1):31. doi: 10.1186/s13041-024-01105-6.
6
WDR45 contributes to neurodegeneration through regulation of ER homeostasis and neuronal death.WDR45 通过调节内质网稳态和神经元死亡促进神经退行性变。
Autophagy. 2020 Mar;16(3):531-547. doi: 10.1080/15548627.2019.1630224. Epub 2019 Jun 23.
7
Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.受损的脂噬诱导小胶质细胞脂滴积累导致糖尿病相关认知障碍中 TREM1 的积累。
Autophagy. 2023 Oct;19(10):2639-2656. doi: 10.1080/15548627.2023.2213984. Epub 2023 May 19.
8
TP53INP2 contributes to autophagosome formation by promoting LC3-ATG7 interaction.TP53INP2 通过促进 LC3-ATG7 相互作用促进自噬体形成。
Autophagy. 2019 Aug;15(8):1309-1321. doi: 10.1080/15548627.2019.1580510. Epub 2019 Feb 20.
9
Autophagy for the quality control of adult hippocampal neural stem cells.自噬对成年海马神经干细胞的质量控制
Brain Res. 2016 Oct 15;1649(Pt B):166-172. doi: 10.1016/j.brainres.2016.02.048. Epub 2016 Mar 9.
10
Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin).PIK3C3 的自噬调控和蛋白激酶活性通过对 SCIN（scinderin）的负调控控制着支持细胞极性。
Autophagy. 2023 Nov;19(11):2934-2957. doi: 10.1080/15548627.2023.2235195. Epub 2023 Jul 14.

引用本文的文献

1
Molecular Mechanism of Antidepressant Effects of Active Ingredients in Traditional Chinese Medicine: The Role of Autophagy.中药活性成分抗抑郁作用的分子机制：自噬的作用
Alpha Psychiatry. 2025 Aug 11;26(4):45685. doi: 10.31083/AP45685. eCollection 2025 Aug.
2
Autophagy-Unlocking New Dimensions in the Pathology and Treatment of Depression.自噬——开启抑郁症病理学与治疗的新维度
Cells. 2025 May 28;14(11):795. doi: 10.3390/cells14110795.
3
Influence of Sevoflurane Postconditioning on Hypoxic-Ischemic Brain Injury via Nrf2-Regulated Ferroptosis in Neonatal Rats.

本文引用的文献

1
Phosphorylation of p62 by AMP-activated protein kinase mediates autophagic cell death in adult hippocampal neural stem cells.AMP激活的蛋白激酶对p62的磷酸化作用介导成年海马神经干细胞的自噬性细胞死亡。
J Biol Chem. 2017 Aug 18;292(33):13795-13808. doi: 10.1074/jbc.M117.780874. Epub 2017 Jun 27.
2
Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors.Semaphorin7A 在成年海马神经发生中的阶段特异性功能依赖于不同的受体。
Nat Commun. 2017 Mar 10;8:14666. doi: 10.1038/ncomms14666.
3
Mediation of Autophagic Cell Death by Type 3 Ryanodine Receptor (RyR3) in Adult Hippocampal Neural Stem Cells.
七氟醚后处理通过Nrf2调控的铁死亡对新生大鼠缺氧缺血性脑损伤的影响
Anesth Analg. 2025 May 16;141(3):648-59. doi: 10.1213/ANE.0000000000007547.
4
Psychological stress-induced systemic corticosterone directly sabotages intestinal stem cells and exacerbates colitis.心理应激诱导的全身性皮质酮直接破坏肠道干细胞并加剧结肠炎。
Cell Discov. 2025 May 13;11(1):46. doi: 10.1038/s41421-025-00796-y.
5
Antidepressant effect of Radix bupleuri - Radix paeoniae alba herb pair on chronic unpredictable mild stress rats based on cortical metabolomics.基于皮质代谢组学探讨柴胡-白芍药对慢性不可预测性温和应激大鼠的抗抑郁作用
BMC Complement Med Ther. 2025 May 10;25(1):168. doi: 10.1186/s12906-025-04898-8.
6
Implications of neurogenesis in depression through BDNF: rodent models, regulatory pathways, gut microbiota, and potential therapy.脑源性神经营养因子介导的神经发生在抑郁症中的意义：啮齿动物模型、调控途径、肠道微生物群及潜在治疗方法
Mol Psychiatry. 2025 May 9. doi: 10.1038/s41380-025-03044-7.
7
Neural stem cell-specific deletion of Atg7 alleviates hippocampal dysfunction and neuronal alterations induced by chronic restraint stress.Atg7在神经干细胞中的特异性缺失可减轻慢性束缚应激诱导的海马功能障碍和神经元改变。
Mol Brain. 2025 Mar 21;18(1):25. doi: 10.1186/s13041-025-01189-8.
8
Atg5 in microglia regulates sex-specific effects on postnatal neurogenesis in Alzheimer's disease.小胶质细胞中的自噬相关蛋白5（Atg5）调节阿尔茨海默病中对产后神经发生的性别特异性影响。
NPJ Aging. 2025 Mar 16;11(1):18. doi: 10.1038/s41514-025-00209-0.
9
Sex in aging matters: exercise and chronic stress differentially impact females and males across the lifespan.衰老过程中的性别差异至关重要：运动和慢性应激在整个生命周期中对女性和男性的影响有所不同。
Front Aging Neurosci. 2025 Jan 15;16:1508801. doi: 10.3389/fnagi.2024.1508801. eCollection 2024.
10
The Critical Role of Autophagy and Phagocytosis in the Aging Brain.自噬和吞噬作用在衰老大脑中的关键作用
Int J Mol Sci. 2024 Dec 25;26(1):57. doi: 10.3390/ijms26010057.
3型雷诺丁受体（RyR3）介导成年海马神经干细胞的自噬性细胞死亡
Front Cell Neurosci. 2016 May 6;10:116. doi: 10.3389/fncel.2016.00116. eCollection 2016.
4
Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy.三类磷脂酰肌醇和磷脂酰肌醇3激酶在自噬中的差异调节功能
Autophagy. 2015;11(10):1711-28. doi: 10.1080/15548627.2015.1043076.
5
Regulation of autophagic cell death by glycogen synthase kinase-3β in adult hippocampal neural stem cells following insulin withdrawal.胰岛素撤除后糖原合酶激酶-3β对成年海马神经干细胞自噬性细胞死亡的调控
Mol Brain. 2015 May 19;8:30. doi: 10.1186/s13041-015-0119-9.
6
Molecular mechanisms in the regulation of adult neurogenesis during stress.应激状态下调节成年神经发生的分子机制。
Nat Rev Neurosci. 2015 Apr;16(4):189-200. doi: 10.1038/nrn3855.
7
CRISPR-Cas9 knockin mice for genome editing and cancer modeling.用于基因组编辑和癌症建模的CRISPR-Cas9基因敲入小鼠
Cell. 2014 Oct 9;159(2):440-55. doi: 10.1016/j.cell.2014.09.014. Epub 2014 Sep 25.
8
Die another way--non-apoptotic mechanisms of cell death.以另一种方式死亡——细胞死亡的非凋亡机制。
J Cell Sci. 2014 May 15;127(Pt 10):2135-44. doi: 10.1242/jcs.093575.
9
Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.SGK1 激酶在应激、抑郁和糖皮质激素对海马神经发生影响中的作用。
Proc Natl Acad Sci U S A. 2013 May 21;110(21):8708-13. doi: 10.1073/pnas.1300886110. Epub 2013 May 6.
10
Glucocorticoids orchestrate divergent effects on mood through adult neurogenesis.糖皮质激素通过成人神经发生来协调对情绪的不同影响。
J Neurosci. 2013 Feb 13;33(7):2961-72. doi: 10.1523/JNEUROSCI.3878-12.2013.