CUMS induces depressive-like behaviors and cognition impairment by activating the ERS-NLRP3 signaling pathway in mice.

Autor:	Hao R; The First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Neurorestoratology, Weihui, Henan 453100, China; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China., Gao X; School of Nursing, Xinxiang Medical University, Xinxiang, Henan 453002, China., Lu Q; The First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Neurorestoratology, Weihui, Henan 453100, China., Zhao T; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China., Lu X; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China., Zhang F; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China; Henan Engineering Research Center of Physical Diagnostics and Treatment Technology for the Mental and Neurological Diseases, Xinxiang, Henan 453002, China., Pei Y; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China., Lang J; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China., Liu H; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China; Henan Engineering Research Center of Physical Diagnostics and Treatment Technology for the Mental and Neurological Diseases, Xinxiang, Henan 453002, China., Song J; The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Henan Key Lab of Biological Psychiatry, Xinxiang, Henan 453002, China; Henan Engineering Research Center of Physical Diagnostics and Treatment Technology for the Mental and Neurological Diseases, Xinxiang, Henan 453002, China. Electronic address: songjg62@126.com., Zhang Z; The First Affiliated Hospital of Xinxiang Medical University, Henan Key Laboratory of Neurorestoratology, Weihui, Henan 453100, China. Electronic address: zzhui816@126.com.
Jazyk:	angličtina
Zdroj:	Journal of affective disorders [J Affect Disord] 2024 Oct 06; Vol. 369, pp. 547-558. Date of Electronic Publication: 2024 Oct 06.
DOI:	10.1016/j.jad.2024.10.001
Abstrakt:	Background and Objective: Endoplasmic reticulum stress (ERS), as a primary defense mechanism against stress, is closely related to mental disorders, but its pathogenesis is still unclear. This research seeks to explore the influence of ERS-nucleotide-bound oligomerized domain-like receptor protein 3 (NLRP3) signaling on mice's depressive-like behaviors and cognitive impairment. Design and Method: We carried out a study on 32 male C57BL/6J mice to investigate how chronic unpredictable mild stress (CUMS) can give rise to depressive-like behaviors and cognitive dysfunction, randomly dividing them into control, model, inhibitor, and agonist groups. We utilized ELISA to quantify dopamine (DA) and 5-hydroxytryptamine (5-HT) levels. Using Nissl and hematoxylin and eosin (H&E) staining, we assessed the number and morphology of hippocampal neurons and cells. Western blot and immunofluorescence staining detected the changes in ERS and inflammation-related pathways in the hippocampus. Results: CUMS could induce ERS and activate NLRP3 inflammasome, causing neuronal damage and histopathological changes, eventually leading to depressive-like behaviors and cognitive impairment in mice. The abnormal activation of NLRP3 inflammasome could be restored by ERS blocker 4-phenyl butyric acid (PBA), thus reducing neuronal damage, and ameliorating depressive-like behaviors and cognitive disorder in mice. Conclusion: Our study demonstrates a previously unknown link between ERS and NLRP3 inflammasome in CUMS mice. The ERS-NLRP3 signaling pathway may be activated by CUMS, potentially resulting in mice exhibiting depressive-like behaviors and cognitive dysfunction. Theoretical foundations for elucidating the pathogenesis of depression, as well as its prevention and treatment, will be established through the results. Competing Interests: Declaration of competing interest The authors hereby state that they do not have any conflicts of interest. (Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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