Hippocampal GPR35 Participates in the Pathogenesis of Cognitive Deficits and Emotional Alterations Induced by Aß1-42 in Mice.
Mol Neurobiol
; 2024 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-38878116
ABSTRACT
The amyloid-beta (Aß) aggregation in Alzheimer's disease (AD) triggers neuroinflammation, and neurodegeneration, which lead to cognitive deficits along with other neuropsychiatric symptoms, including depression and anxiety. G protein-coupled receptor 35 (GPR35) is expressed in the brain and is involved in metabolic stresses. However, the role of GPR35 in AD pathogenesis remains unknown. Herein, pharmacological blockade, shRNA-mediated knockdown or knockout of GPR35 was performed to investigate the role and mechanisms of GPR35 in Aß1-42-induced cognitive impairment and emotional alterations in mice. A series of behavioral, histopathological, and biochemical tests were performed in mice. Our results showed that hippocampal GPR35 expression was significantly increased in Aß1-42-induced and APP/PS1 AD mouse models. Pharmacological blockade or knockdown of GPR35 ameliorated cognitive impairment and emotional alterations induced by Aß1-42 in mice. We also found that blockade or knockdown of GPR35 decreased the accumulation of Aß, and improved neuroinflammation, cholinergic system deficiency, and neuronal apoptosis via the RhoA/ROCK2 pathway in Aß1-42-treaed mice. However, activation of GPR35 aggravates Aß1-42-induced cognitive deficits and emotional alterations in mice. In addition, genetic deletion of GPR35 protects against the Aß1-42-induced cognitive deficits and emotional alterations in mice. Moreover, GPR35 could bind to TLR4. These results indicate that GPR35 participates in the pathogenesis of cognitive deficits and emotional alterations induced by Aß1-42 in mice, suggesting that GPR35 could be a potential therapeutic target for AD.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
Mol Neurobiol
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China