• 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

产前白细胞介素 6 水平升高会增加谷氨酸能突触密度，并破坏后代海马体的连接。

Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.

机构信息

Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy.

IRCCS Humanitas Research Hospital, via Manzoni 56, 20089 Rozzano, Milan, Italy; Institute of Neuroscience - National Research Council, 20139 Milan, Italy.

出版信息

Immunity. 2021 Nov 9;54(11):2611-2631.e8. doi: 10.1016/j.immuni.2021.10.006.

DOI:10.1016/j.immuni.2021.10.006
PMID:34758338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8585508/
Abstract

Early prenatal inflammatory conditions are thought to be a risk factor for different neurodevelopmental disorders. Maternal interleukin-6 (IL-6) elevation during pregnancy causes abnormal behavior in offspring, but whether these defects result from altered synaptic developmental trajectories remains unclear. Here we showed that transient IL-6 elevation via injection into pregnant mice or developing embryos enhanced glutamatergic synapses and led to overall brain hyperconnectivity in offspring into adulthood. IL-6 activated synaptogenesis gene programs in glutamatergic neurons and required the transcription factor STAT3 and expression of the RGS4 gene. The STAT3-RGS4 pathway was also activated in neonatal brains during poly(I:C)-induced maternal immune activation, which mimics viral infection during pregnancy. These findings indicate that IL-6 elevation at early developmental stages is sufficient to exert a long-lasting effect on glutamatergic synaptogenesis and brain connectivity, providing a mechanistic framework for the association between prenatal inflammatory events and brain neurodevelopmental disorders.

摘要

早期产前炎症被认为是多种神经发育障碍的危险因素。怀孕期间母体白细胞介素-6（IL-6）的升高会导致后代出现异常行为，但这些缺陷是否是由于突触发育轨迹的改变所致尚不清楚。在这里，我们发现通过向怀孕小鼠或发育中的胚胎注射短暂升高 IL-6 会增强谷氨酸能突触，并导致后代成年后大脑整体过度连接。IL-6 激活了谷氨酸能神经元中的突触发生基因程序，需要转录因子 STAT3 和 RGS4 基因的表达。在多聚（I：C）诱导的母体免疫激活期间，新生大脑中也会激活 STAT3-RGS4 通路，这模拟了怀孕期间的病毒感染。这些发现表明，在早期发育阶段升高 IL-6 足以对谷氨酸能突触发生和大脑连接产生持久影响，为产前炎症事件与大脑神经发育障碍之间的关联提供了一个机制框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/8af7e8ad81e1/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/29333343c638/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/6936356960bd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/05203d5d561b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/84f0a363931b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/f094986a31da/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/03ee0c1f4ff2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/785541fdc4cb/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/8af7e8ad81e1/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/29333343c638/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/6936356960bd/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/05203d5d561b/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/84f0a363931b/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/f094986a31da/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/03ee0c1f4ff2/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/785541fdc4cb/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e31f/8585508/8af7e8ad81e1/gr7.jpg

相似文献

1
Prenatal interleukin 6 elevation increases glutamatergic synapse density and disrupts hippocampal connectivity in offspring.产前白细胞介素 6 水平升高会增加谷氨酸能突触密度，并破坏后代海马体的连接。
Immunity. 2021 Nov 9;54(11):2611-2631.e8. doi: 10.1016/j.immuni.2021.10.006.
2
Late prenatal immune activation causes hippocampal deficits in the absence of persistent inflammation across aging.产前晚期免疫激活会导致海马体缺陷，且在整个衰老过程中不存在持续性炎症。
J Neuroinflammation. 2015 Nov 25;12:221. doi: 10.1186/s12974-015-0437-y.
3
Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies.产前免疫激活导致海马突触缺陷，而无明显小胶质细胞异常。
Brain Behav Immun. 2016 Jul;55:25-38. doi: 10.1016/j.bbi.2015.09.015. Epub 2015 Sep 25.
4
Exposure to gestational diabetes mellitus induces neuroinflammation, derangement of hippocampal neurons, and cognitive changes in rat offspring.暴露于妊娠期糖尿病会诱发神经炎症、海马神经元紊乱以及大鼠后代的认知变化。
J Neuroinflammation. 2017 Apr 7;14(1):80. doi: 10.1186/s12974-017-0859-9.
5
Maternal immune activation by poly I:C induces expression of cytokines IL-1β and IL-13, chemokine MCP-1 and colony stimulating factor VEGF in fetal mouse brain.聚肌苷酸-聚胞苷酸（poly I:C）诱导的母体免疫激活可诱导胎鼠大脑中细胞因子白细胞介素-1β和白细胞介素-13、趋化因子单核细胞趋化蛋白-1 和集落刺激因子血管内皮生长因子的表达。
J Neuroinflammation. 2012 Apr 30;9:83. doi: 10.1186/1742-2094-9-83.
6
Exercise Reverses Behavioral and Synaptic Abnormalities after Maternal Inflammation.运动可逆转母体炎症后的行为和突触异常。
Cell Rep. 2019 Jun 4;27(10):2817-2825.e5. doi: 10.1016/j.celrep.2019.05.015.
7
Brain region-specific alterations in gene expression trajectories in the offspring born from influenza A virus infected mice.流感病毒感染小鼠所生后代中脑区基因表达轨迹的特异性改变。
Brain Behav Immun. 2024 Aug;120:488-498. doi: 10.1016/j.bbi.2024.06.025. Epub 2024 Jun 24.
8
Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function.小胶质细胞的产前激活会导致谷氨酸能突触功能的延迟损伤。
PLoS One. 2008 Jul 9;3(7):e2595. doi: 10.1371/journal.pone.0002595.
9
Brain inflammation induces post-synaptic changes during early synapse formation in adult-born hippocampal neurons.脑炎症在成年海马神经元早期突触形成过程中诱导突触后变化。
Exp Neurol. 2013 Dec;250:176-88. doi: 10.1016/j.expneurol.2013.09.005. Epub 2013 Sep 15.
10
Duloxetine prevents the effects of prenatal stress on depressive-like and anxiety-like behavior and hippocampal expression of pro-inflammatory cytokines in adult male offspring rats.度洛西汀可预防产前应激对成年雄性子代大鼠抑郁样和焦虑样行为以及海马促炎细胞因子表达的影响。
Int J Dev Neurosci. 2016 Dec;55:41-48. doi: 10.1016/j.ijdevneu.2016.09.005. Epub 2016 Sep 13.

引用本文的文献

1
FMRP regulation of STAT3-MYC signaling is critical for adult hippocampal neurogenesis and cognitive flexibility.脆性X智力低下蛋白（FMRP）对信号转导及转录激活因子3（STAT3）- 原癌基因c-MYC（MYC）信号通路的调控对成体海马神经发生和认知灵活性至关重要。
Cell Death Differ. 2025 Jul 19. doi: 10.1038/s41418-025-01546-z.
2
Maternal stressors disrupt mouse placental proteome and fetal brain development in a sex-specific fashion through inflammation and oxidative stress.母体应激源通过炎症和氧化应激以性别特异性方式破坏小鼠胎盘蛋白质组和胎儿大脑发育。
Mol Psychiatry. 2025 Jul 10. doi: 10.1038/s41380-025-03090-1.
3
Sabinene Inhibits Lipopolysaccharide-Induced Memory Decline by Enhancing Cholinergic Function, Decreasing Molybdenum Enzymes, and Suppressing Oxidative Stress and Neuroinflammation.

本文引用的文献

1
Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring.产前母体感染可促进子代组织特异性免疫和炎症反应。
Science. 2021 Aug 27;373(6558). doi: 10.1126/science.abf3002.
2
Is IL-6 a key cytokine target for therapy in COVID-19?白细胞介素-6 是 COVID-19 治疗的关键细胞因子靶点吗？
Nat Rev Immunol. 2021 Jun;21(6):337-339. doi: 10.1038/s41577-021-00553-8.
3
Latrophilin GPCR signaling mediates synapse formation.拉托菲林 GPCR 信号转导介导突触形成。
桧烯通过增强胆碱能功能、降低钼酶、抑制氧化应激和神经炎症来抑制脂多糖诱导的记忆衰退。
Neurotox Res. 2025 Jun 5;43(3):26. doi: 10.1007/s12640-025-00750-6.
4
Neuronal hyperexcitability in dystrophin-deficient mdx hippocampal neurons: the importance of interleukin-6 and GABAergic regulation.肌营养不良蛋白缺乏的mdx海马神经元中的神经元过度兴奋：白细胞介素-6和GABA能调节的重要性。
Sci Rep. 2025 May 30;15(1):18984. doi: 10.1038/s41598-025-00880-z.
5
An ace in the hole? Opportunities and limits of using mice to understand schizophrenia neurobiology.一张王牌？利用小鼠理解精神分裂症神经生物学的机遇与局限
Mol Psychiatry. 2025 May 22. doi: 10.1038/s41380-025-03060-7.
6
The roles of immune factors in neurodevelopment.免疫因子在神经发育中的作用。
Front Cell Neurosci. 2025 Apr 10;19:1451889. doi: 10.3389/fncel.2025.1451889. eCollection 2025.
7
Decreased hippocampal neurite density in late middle-aged adults following prenatal exposure to higher levels of maternal inflammation.产前暴露于较高水平的母体炎症后，中年后期成年人海马体神经突密度降低。
bioRxiv. 2025 Mar 25:2024.10.01.616156. doi: 10.1101/2024.10.01.616156.
8
Meningeal lymphatics-microglia axis regulates synaptic physiology.脑膜淋巴管-小胶质细胞轴调节突触生理学。
Cell. 2025 May 15;188(10):2705-2719.e23. doi: 10.1016/j.cell.2025.02.022. Epub 2025 Mar 21.
9
The Role of Neuroinflammation and Network Anomalies in Drug-Resistant Epilepsy.神经炎症和网络异常在耐药性癫痫中的作用
Neurosci Bull. 2025 May;41(5):881-905. doi: 10.1007/s12264-025-01348-w. Epub 2025 Feb 24.
10
Prenatal Inflammation Reprograms Hypothalamic-Pituitary-Gonadal Axis Development in Female Rats.产前炎症重编程雌性大鼠下丘脑-垂体-性腺轴的发育。
Inflammation. 2025 Feb 5. doi: 10.1007/s10753-025-02243-2.
Elife. 2021 Mar 1;10:e65717. doi: 10.7554/eLife.65717.
4
Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants.早期母婴护理可恢复早产婴儿的LINE-1甲基化并促进其神经发育。
BMC Med. 2021 Feb 5;19(1):42. doi: 10.1186/s12916-020-01896-0.
5
Pregnancy and COVID-19.妊娠与 COVID-19。
Physiol Rev. 2021 Jan 1;101(1):303-318. doi: 10.1152/physrev.00024.2020. Epub 2020 Sep 24.
6
Cortical Excitation:Inhibition Imbalance Causes Abnormal Brain Network Dynamics as Observed in Neurodevelopmental Disorders.皮层兴奋：抑制失衡导致神经发育障碍中观察到的异常脑网络动力学。
Cereb Cortex. 2020 Jul 30;30(9):4922-4937. doi: 10.1093/cercor/bhaa084.
7
Cytokine release syndrome in severe COVID-19.重症新型冠状病毒肺炎中的细胞因子释放综合征
Science. 2020 May 1;368(6490):473-474. doi: 10.1126/science.abb8925. Epub 2020 Apr 17.
8
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.中国武汉成人 COVID-19 住院患者的临床病程和死亡危险因素：一项回顾性队列研究。
Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11.
9
Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner.IL-6 依赖性方式下，再殖化小胶质细胞促进大脑修复。
Cell. 2020 Mar 5;180(5):833-846.e16. doi: 10.1016/j.cell.2020.02.013.
10
Decoding the development of the human hippocampus.解码人类海马体的发育。
Nature. 2020 Jan;577(7791):531-536. doi: 10.1038/s41586-019-1917-5. Epub 2020 Jan 15.