AQP4 is upregulated in schizophrenia and Its inhibition attenuates MK-801-induced schizophrenia-like behaviors in mice.

Autor: Nie FY; Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China; Shaanxi Collaborative Innovation Center of TCM Technologies and Devices, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Jin RY; Shaanxi Key Lab Basic & New Herbal Medicament Research Center, College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Wu SS; School of Basic Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Yuan W; Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Wu YW; Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Xue SM; Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China., Yang XH; Shaanxi Collaborative Innovation Center of TCM Technologies and Devices, Shaanxi University of Chinese Medicine, Xianyang 712046, China. Electronic address: yxh1.0@163.com., Qiao HF; Shaanxi Key Laboratory of Acupuncture and Medicine, Shaanxi University of Chinese Medicine, Xianyang 712046, China. Electronic address: 1511006@sntcm.edu.cn.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2024 Oct 18; Vol. 475, pp. 115220. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.bbr.2024.115220
Abstrakt: Background: The pathophysiology and molecular mechanisms of schizophrenia (SCZ) remain unclear, and the effective treatment resources are still limited. The goal of this study is to identify the expression of AQP4 in SCZ patients and explore whether AQP4 inhibition could ameliorate schizophrenia-like behaviors and its mechanisms.
Methods: Microarray datasets of PFC compared with healthy control were searched in the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were analyzed with the GEO2R online tool. The Venny online tool and metascape online software were used to identify common abnormally expressed genes and conduct cell type signature enrichment analysis. SCZ mouse models were induced with MK-801, an NMDA receptor antagonist (intraperitoneal injection, 0.1 mg/kg/day for 7 days), and C6 cell models were treated with 100 μM MK-801. RT-qPCR, Western Blotting, and immunofluorescence were employed to determine the expression of AQP4, proinflammatory cytokines, and GFAP. Open field tests and social interaction tests were performed to evaluate the schizophrenia-like behaviors.
Results: Bioinformatics analysis identified upregulation of AQP4 in the PFC of SCZ patients compared with healthy controls. Cell type signature enrichment analysis showed that all three DEGs lists were strongly enriched in the FAN EMBRYONIC CTX ASTROCYTE 2 category. Upregulation of AQP4 was also observed in MK-801-treated C6 cells and the PFC of MK-801-induced SCZ mouse model. Moreover, AQP4 inhibition with TGN-020 (an inhibitor of AQP4) improved anxiety-like behavior and social novelty preference defects in MK-801-treated mice. AQP4 inhibition also reduced the expression of IL-1β, IL-6, and TNF-α in MK-801-treated C6 cells and mouse model.
Conclusions: AQP4 is upregulated in the PFC of SCZ patients compared with healthy controls. AQP4 inhibition could alleviate the anxiety-like behavior and social novelty defects in MK-801-treated mice, this may be due to the role of AQP4 in the regulation of the expression of proinflammatory cytokines.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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