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

Animals Male Circadian Rhythm / physiology Mice Bipolar Disorder / metabolism Mice, Transgenic Synapses / metabolism Hippocampus / metabolism NIMA-Related Kinases / metabolism Emotions / physiology Behavior, Animal Humans Dendritic Spines / metabolism Pyramidal Cells / metabolism Lithium / pharmacology Mice, Inbred C57BL Genome-Wide Association Study Anxiety / metabolism Disease Models, Animal

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 Oct 2024
Historique:
received: 07 03 2024
accepted: 16 10 2024
medline: 25 10 2024
pubmed: 25 10 2024
entrez: 25 10 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-024-53585-8 PMID: 39448584
pubmed: 39448584
doi: 10.1038/s41467-024-53585-8
pii: 10.1038/s41467-024-53585-8
doi:

Substances chimiques

NIMA-Related Kinases EC 2.7.11.1
Lithium 9FN79X2M3F

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

9180

Informations de copyright

© 2024. The Author(s).

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Auteurs

Zhi-Hui 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.

Xin 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.

Chu-Yi 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.
ORCID: 0000-0003-3369-1883

Qing 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.

Miao 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.

Zhong-Li 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.

Yingqi Guo (Y)

Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Guolan Ma (G)

Institutional Center for Shared Technologies and Facilities of Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.

Chao-Hao 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.

Lei 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.

Hong 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.

Chuang 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.
ORCID: 0000-0002-3816-230X

Ming 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.
ORCID: 0000-0002-8197-6552

Xiao 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.
ORCID: 0000-0003-3608-6208

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes chronobiologiques › Périodicité › Rythme circadien › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Troubles mentaux › Troubles de l'humeur › Troubles bipolaires et apparentés › Trouble bipolaire › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Cortex cérébral › Hippocampe › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Kinases apparentées à NIMA › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Émotions › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Cellules › Neurones › Dendrites › Épines dendritiques › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Cellules › Neurones › Cellules pyramidales › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Produits chimiques inorganiques › Métaux › Métaux légers › Lithium › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Émotions › Anxiété › NEK4 modulates circadian fluctuations of...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › NEK4 modulates circadian fluctuations of...