Social isolation impairs cognition via Aß-mediated synaptic dysfunction.
Transl Psychiatry
; 14(1): 380, 2024 Sep 18.
Article
em En
| MEDLINE
| ID: mdl-39294141
ABSTRACT
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 Aß 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 Aß 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 Aß toxicity and induces behavioural deficits. Down-regulation of BACE1 may be a promising strategy for preventing SI-induced cognitive impairments.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isolamento Social
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Camundongos Transgênicos
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Peptídeos beta-Amiloides
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Ácido Aspártico Endopeptidases
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Secretases da Proteína Precursora do Amiloide
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Disfunção Cognitiva
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Camundongos Endogâmicos C57BL
Limite:
Animals
Idioma:
En
Revista:
Transl Psychiatry
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos