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真核生物翻译起始因子4E(eIF4E)的过表达降低小鼠催产素水平并诱发社会认知行为障碍。

The Overexpression of eIF4E Decreases Oxytocin Levels and Induces Social Cognitive Behavioral Disorders in Mice.

作者信息

Wang Juan, Chen Sijie, Zhao Miao, Zheng Lizhen, Huang Xinxin, Hong Xin, Kang Jie, Ou Ping, Huang Longsheng

机构信息

College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China.

Child Health Center, Fujian Maternity and Child Health Hospital, Fuzhou 350001, China.

出版信息

eNeuro. 2024 Dec 10;11(12). doi: 10.1523/ENEURO.0387-24.2024. Print 2024 Dec.

DOI:10.1523/ENEURO.0387-24.2024
PMID:39557567
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11633592/
Abstract

Overexpression of the eukaryotic initiation factor 4E () gene has been associated with excessive stereotypic behaviors and reduced sociability, which manifest as autism-like social cognitive deficits. However, the precise mechanisms by which overexpression insufficiently induces these autism-like behaviors and the specific brain regions implicated remain insufficiently understood. Oxytocin (OXT), a neurotransmitter known for its role in social behavior, has been proposed to modulate certain autism-related symptoms by influencing microglial function and attenuating neuroinflammation. Nonetheless, the contributions of the hippocampus and oxytocin in the content of overexpression-induced autistic behaviors remain elucidated. To investigate this issue, researchers utilized the three-chamber social interaction test, the open-field test, and the Morris water maze to evaluate the social cognitive behaviors of the two groups of mice. Additionally, ELISA, immunofluorescence, Western blotting, and qRT-PCR were employed to quantify oxytocin levels and assess hippocampal microglial activation. The results indicate that overexpression of in mice is associated with significant impairments in social cognition, alongside pronounced marked hyperactivation of hippocampal microglia.

摘要

真核生物起始因子4E()基因的过表达与过度刻板行为和社交能力下降有关,这些表现为类似自闭症的社会认知缺陷。然而,过表达不足以诱导这些类似自闭症行为的确切机制以及所涉及的特定脑区仍未得到充分理解。催产素(OXT)是一种以其在社会行为中的作用而闻名的神经递质,有人提出它通过影响小胶质细胞功能和减轻神经炎症来调节某些与自闭症相关的症状。尽管如此,海马体和催产素在过表达诱导的自闭症行为中的作用仍有待阐明。为了研究这个问题,研究人员利用三室社交互动测试、旷场测试和莫里斯水迷宫来评估两组小鼠的社会认知行为。此外,采用酶联免疫吸附测定(ELISA)、免疫荧光、蛋白质免疫印迹法(Western blotting)和定量逆转录聚合酶链反应(qRT-PCR)来量化催产素水平并评估海马体小胶质细胞的激活情况。结果表明,小鼠中的过表达与社会认知的显著损害以及海马体小胶质细胞的明显过度激活有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/e6ae9cc8de62/eneuro-11-ENEURO.0387-24.2024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/a8017dc93cd2/eneuro-11-ENEURO.0387-24.2024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/1620b0a4e747/eneuro-11-ENEURO.0387-24.2024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/e6ae9cc8de62/eneuro-11-ENEURO.0387-24.2024-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/a8017dc93cd2/eneuro-11-ENEURO.0387-24.2024-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/1620b0a4e747/eneuro-11-ENEURO.0387-24.2024-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a415/11633592/e6ae9cc8de62/eneuro-11-ENEURO.0387-24.2024-g003.jpg

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IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice.IL-6 通过上调自闭症小鼠海马神经元中的 GRPR 增强 PI3K-AKT/mTOR-GSK-3β 的激活。
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