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小鼠母体免疫激活会破坏胎儿大脑中的蛋白质稳态。

Maternal immune activation in mice disrupts proteostasis in the fetal brain.

作者信息

Kalish Brian T, Kim Eunha, Finander Benjamin, Duffy Erin E, Kim Hyunju, Gilman Casey K, Yim Yeong Shin, Tong Lilin, Kaufman Randal J, Griffith Eric C, Choi Gloria B, Greenberg Michael E, Huh Jun R

机构信息

Department of Neurobiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.

出版信息

Nat Neurosci. 2021 Feb;24(2):204-213. doi: 10.1038/s41593-020-00762-9. Epub 2020 Dec 23.

DOI:10.1038/s41593-020-00762-9
PMID:33361822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7854524/
Abstract

Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.

摘要

孕期母体感染和炎症与后代神经发育障碍有关，但对于这一流行病学现象背后的分子机制却知之甚少。在此，我们利用单细胞RNA测序来分析小鼠胎儿大脑对母体免疫激活（MIA）的转录变化，并确定了与mRNA翻译、核糖体生物合成和应激信号相关的细胞途径中的扰动。我们发现，MIA以白细胞介素-17a依赖的方式激活雄性而非雌性MIA后代的综合应激反应（ISR），这降低了整体mRNA翻译并改变了新生蛋白质组的合成。此外，阻断ISR激活可预防MIA雄性后代的行为异常以及增加皮质神经活动。我们的数据表明，ISR的性别特异性激活导致了与母体炎症相关的神经发育障碍。

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本文引用的文献

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2
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Eur J Neurosci. 2020 Jul;52(1):2614-2626. doi: 10.1111/ejn.14671. Epub 2020 Jan 20.
3
Maternal and early postnatal immune activation produce sex-specific effects on autism-like behaviors and neuroimmune function in mice.
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Comput Struct Biotechnol J. 2025 Jul 12;27:3127-3136. doi: 10.1016/j.csbj.2025.07.015. eCollection 2025.
4
Cohort protocol: risk assessment of maternal inflammation and early brain development in infants and young children based on multi-source data modeling.队列研究方案：基于多源数据建模的婴幼儿母亲炎症与早期脑发育风险评估
Front Public Health. 2025 Jul 14;13:1530285. doi: 10.3389/fpubh.2025.1530285. eCollection 2025.
5
Etiologies underlying sex bias in autism spectrum disorder: a narrative review of preclinical rodent models.自闭症谱系障碍中性别偏见的潜在病因：对临床前啮齿动物模型的叙述性综述。
Ewha Med J. 2024 Apr;47(2):e18. doi: 10.12771/emj.2024.e18. Epub 2024 Apr 30.
6
PROTOCOL: Association of Antenatal Cytokine Concentrations With Neurodevelopmental Disorders of the Offspring: A Scoping Review.方案：产前细胞因子浓度与后代神经发育障碍的关联：一项范围综述。
Campbell Syst Rev. 2025 Jul 7;21(3):e70053. doi: 10.1002/cl2.70053. eCollection 2025 Sep.
7
The role of interleukin-17 in neurological disorders.白细胞介素-17在神经疾病中的作用。
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5
Single-cell transcriptomic profiling of the aging mouse brain.单细胞转录组谱分析衰老小鼠大脑。
Nat Neurosci. 2019 Oct;22(10):1696-1708. doi: 10.1038/s41593-019-0491-3. Epub 2019 Sep 24.
6
Erroneous inference based on a lack of preference within one group: Autism, mice, and the social approach task.基于一个群体内缺乏偏好的错误推断：自闭症、老鼠和社交接近任务。
Autism Res. 2019 Aug;12(8):1171-1183. doi: 10.1002/aur.2154. Epub 2019 Jun 11.
7
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Cell Syst. 2019 Apr 24;8(4):281-291.e9. doi: 10.1016/j.cels.2018.11.005. Epub 2019 Apr 3.
8
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9
Single-cell transcriptomic analysis of mouse neocortical development.单细胞转录组分析小鼠新皮层发育。
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10
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Dev Neurobiol. 2019 Jan;79(1):60-74. doi: 10.1002/dneu.22653. Epub 2018 Nov 28.