NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.

Autor: Yang ZH; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Cai X; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Zhang CY; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Zhang Q; Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.; School of Basic Medical Science, Health Science Center, Ningbo University, Ningbo, Zhejiang, China., Li M; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Ding ZL; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Guo Y; Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Ma G; Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Yang CH; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China., Guo L; Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.; School of Basic Medical Science, Health Science Center, Ningbo University, Ningbo, Zhejiang, China., Chang H; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China., Wang C; Zhejiang Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, Zhejiang, China.; School of Basic Medical Science, Health Science Center, Ningbo University, Ningbo, Zhejiang, China., Li M; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. limingkiz@mail.kiz.ac.cn.; Yunnan Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. limingkiz@mail.kiz.ac.cn.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China. limingkiz@mail.kiz.ac.cn.; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. limingkiz@mail.kiz.ac.cn., Xiao X; Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. xiaoxiao2@mail.kiz.ac.cn.; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China. xiaoxiao2@mail.kiz.ac.cn.; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. xiaoxiao2@mail.kiz.ac.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Oct 24; Vol. 15 (1), pp. 9180. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1038/s41467-024-53585-8
Abstrakt: GWASs have linked the 3p21.1 locus, which is associated with the expression levels of NEK4, to bipolar disorder. Here, we use integrative analyses of GWAS statistics and eQTL annotations to establish that elevated NEK4 expression in the hippocampus is associated with an increased risk of bipolar disorder. To further study this association, we generate transgenic male mice that conditionally overexpress NEK4 in the pyramidal neurons of the adult forebrain, or use AAV to overexpress NEK4 in the dorsal hippocampus. Compared to the control mice, male mice of both strains exhibit a shift from a diurnal anxiety state to a nocturnal normal or anxiolytic-like state. Overexpression of NEK4 also affects the circadian fluctuations in dendritic spine morphology and synaptic structure. Furthermore, we show that treatment with lithium ameliorates the effects of NEK4 overexpression in male mice. We then perform phosphoproteomic analyses to demonstrate that the diurnal and nocturnal phosphoproteomic profiles of male control and NEK4 overexpressing mice are different. These results suggest that male mice with different NEK4 expression levels may recapitulate some of the core features observed in patients with bipolar disorder, indicating that interruption of the homeostatic dynamics of synapses may underlie the emotional swings in bipolar disorder.
(© 2024. The Author(s).)
Databáze: MEDLINE
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