Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice

	Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice
	Zhou, BY; Li, ZX; Li, YW; Li, JN; Liu, WT; Liu, XY; Hu, ZB; Zhao, L; Chen, JY; Hu, L; Song, NN; Feng, X; Wang, G; Xu, L; Ding, YQ
	2025
发表期刊	NEUROPSYCHOPHARMACOLOGY
ISSN	0893-133X
摘要	Attention-deficit hyperactivity disorder (ADHD) is a prevalent psychiatric disorder with high heritability, while its etiology and pathophysiology remain unclear. Med23 is a subunit of the Mediator complex, a key regulator of gene expression by linking transcription factors to RNA polymerase II. The mutations of Med23 are associated with several brain diseases including microcephaly, epilepsy and intellectual disability, but its biological roles in brain development and possible behavioral consequence have not been explored in the animal model. In this study, Emx1-Cre mice were used to generate Med23 conditional knockout (Med23 CKO) mice that showed severe hypoplasia of the dentate gyrus (DG) with malformation of the dendritic tree and spines along with impaired short-term synaptic plasticity. Interestingly, Med23 CKO mice exhibited ADHD-like behaviors as shown by hyperactivity, inattention and impulsivity, as well as impaired sensory gating and working memory. Importantly, methylphenidate (MPH), a common drug for ADHD ameliorated these deficits in the CKO mice. Furthermore, we also revealed that the impaired synaptic plasticity was partially restored by MPH in an N-methyl-d-aspartate (NMDA) receptor-dependent way. Collectively, our data demonstrate Med23 deficiency causes DG malformation and ADHD-like behaviors, suggesting a novel mechanism underlying relevant brain diseases.
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/152453/14536
专题	科研部门_学习记忆的分子神经机制（徐林）
推荐引用方式 GB/T 7714	Zhou, BY,Li, ZX,Li, YW,et al. Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice[J]. NEUROPSYCHOPHARMACOLOGY,2025.
APA	Zhou, BY.,Li, ZX.,Li, YW.,Li, JN.,Liu, WT.,...&Ding, YQ.(2025).Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice.NEUROPSYCHOPHARMACOLOGY.
MLA	Zhou, BY,et al."Central Med23 deficiency leads to malformation of dentate gyrus and ADHD-like behaviors in mice".NEUROPSYCHOPHARMACOLOGY (2025).

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