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

	NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice
	Yang, ZH; Cai, X; Zhang, CY; Zhang, Q; Li, M; Ding, ZL; Guo, YQ; Ma, GL; Yang, CH; Guo, L; Chang, H; Wang, C; Li, M; Xiao, X
	2024
发表期刊	NATURE COMMUNICATIONS
卷号	15 期号:1
摘要	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. The expression levels of NEK4 have been associated with bipolar disorder in GWAS. Here, the authors examine the physiological effects of overexpressing NEK4 in the hippocampus of mice, showing that it leads to aberrations in circadian traits.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14455
专题	科研部门_环境与精神健康（肖潇）
推荐引用方式 GB/T 7714	Yang, ZH,Cai, X,Zhang, CY,et al. NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice[J]. NATURE COMMUNICATIONS,2024,15(1).
APA	Yang, ZH.,Cai, X.,Zhang, CY.,Zhang, Q.,Li, M.,...&Xiao, X.(2024).NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.NATURE COMMUNICATIONS,15(1).
MLA	Yang, ZH,et al."NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice".NATURE COMMUNICATIONS 15.1(2024).

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