社会隔离通过 Aβ 介导的突触功能障碍损害认知能力

IF 5.8 1区 医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2024-09-18 DOI:10.1038/s41398-024-03078-5
Fang Huang, Xinghua Liu, Qian Guo, Yacoubou Abdoul Razak Mahaman, Bin Zhang, Jian-Zhi Wang, Hongbin Luo, Rong Liu, Xiaochuan Wang
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引用次数: 0

摘要

社会隔离(SI)是现代世界的一种普遍现象,尤其是在冠状病毒病 2019 年大流行期间,它会导致持久的认知障碍和精神障碍。然而,目前仍不清楚社会隔离如何改变大脑分子并诱发行为功能障碍。在这里,我们报告了 SI 损害 C57BL/6 J 小鼠的认知功能并诱发抑郁样行为,此外还损害突触可塑性并增加 APP 裂解相关酶的水平,从而促进 Aβ 的产生。此外,我们还发现,在 APP/PS1 转基因小鼠中,SI 会加速病理变化和行为缺陷。有趣的是,下调 BACE1 的表达可减轻 SI 诱导的 Aβ 毒性和突触功能障碍。此外,使用 BACE1 shRNA 进行早期干预可阻止 SI 诱导的认知障碍。总之,我们的数据有力地表明,SI 诱导的 BACE1 表达上调介导了 Aβ 的毒性并诱发了行为障碍。下调BACE1可能是预防SI诱导的认知障碍的一种有效策略。
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Social isolation impairs cognition via Aβ-mediated synaptic dysfunction

Social isolation (SI) is a common phenomenon in the modern world, especially during the coronavirus disease 2019 pandemic, and causes lasting cognitive impairments and mental disorders. However, it is still unclear how SI alters molecules in the brain and induces behavioural dysfunctions. Here, we report that SI impairs cognitive function and induces depressive-like behaviours in C57BL/6 J mice, in addition to impairing synaptic plasticity and increasing the levels of APP cleavage-related enzymes, thereby promoting Aβ production. Moreover, we show that in APP/PS1 transgenic mice, SI accelerates pathological changes and behavioural deficits. Interestingly, downregulation of the expression of the BACE1 attenuates SI-induced Aβ toxicity and synaptic dysfunction. Furthermore, early intervention with BACE1 shRNA blocks SI-induced cognitive impairments. Together, our data strongly suggest that SI-induced upregulation of BACE1 expression mediates Aβ toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.

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来源期刊
CiteScore
11.50
自引率
2.90%
发文量
484
审稿时长
23 weeks
期刊介绍: Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.
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