Sex-specific modulation of anxiety-like behavior by forebrain neuronal SMC3 in mice.

IF 6.2 1区医学 Q1 PSYCHIATRY

Translational Psychiatry Pub Date : 2025-08-05 DOI:10.1038/s41398-025-03494-1

Natalia Saleev, Dmitriy Getselter, Evan Elliott

{"title":"Sex-specific modulation of anxiety-like behavior by forebrain neuronal SMC3 in mice.","authors":"Natalia Saleev, Dmitriy Getselter, Evan Elliott","doi":"10.1038/s41398-025-03494-1","DOIUrl":null,"url":null,"abstract":"<p><p>SMC3 is a chromatin binding factor that plays central roles in genome organization and in proper neurodevelopment. Mutations in SMC3 gene (SMC3) induce neurodevelopmental and behavioral phenotypes in humans, including changes in anxiety behavior and self-injury. However, it is not clear what are the exact roles of SMC3 in behavior in adulthood or if its effects are only developmental. Using an adult forebrain excitatory neuron specific Smc3 knockout mouse model, the current study determined specific sex-dependent effects of SMC3 ablation during adulthood. Behavioral tests identified anxiolytic effects of Smc3 knockout in females and anxiogenic effects in males four weeks after initiation of adult knockout. The prefrontal cortex, a regulator of anxiety behavior, also displayed sex-dependent effects in dendritic branching. Transcriptional analysis revealed gene expression effects of Smc3 knockout in males and females, including changes in anxiety-related genes and relevant transcriptional pathways. While effects on anxiety behavior was sex-specific, both males and females developed self-injury behavior at approximately ten weeks after induction of knockout. The current study suggests that neuronal SMC3 modulates anxiety during adulthood in a sex-specific manner.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"266"},"PeriodicalIF":6.2000,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325900/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-025-03494-1","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 0

Abstract

SMC3 is a chromatin binding factor that plays central roles in genome organization and in proper neurodevelopment. Mutations in SMC3 gene (SMC3) induce neurodevelopmental and behavioral phenotypes in humans, including changes in anxiety behavior and self-injury. However, it is not clear what are the exact roles of SMC3 in behavior in adulthood or if its effects are only developmental. Using an adult forebrain excitatory neuron specific Smc3 knockout mouse model, the current study determined specific sex-dependent effects of SMC3 ablation during adulthood. Behavioral tests identified anxiolytic effects of Smc3 knockout in females and anxiogenic effects in males four weeks after initiation of adult knockout. The prefrontal cortex, a regulator of anxiety behavior, also displayed sex-dependent effects in dendritic branching. Transcriptional analysis revealed gene expression effects of Smc3 knockout in males and females, including changes in anxiety-related genes and relevant transcriptional pathways. While effects on anxiety behavior was sex-specific, both males and females developed self-injury behavior at approximately ten weeks after induction of knockout. The current study suggests that neuronal SMC3 modulates anxiety during adulthood in a sex-specific manner.

查看原文本刊更多论文

小鼠前脑神经元SMC3对焦虑样行为的性别特异性调节。

SMC3是一种染色质结合因子，在基因组组织和正常神经发育中起着核心作用。SMC3基因突变（SMC3）诱导人类神经发育和行为表型，包括焦虑行为和自伤行为的改变。然而，目前尚不清楚SMC3在成年期行为中的确切作用，或者它的影响是否只是发育性的。使用成年前脑兴奋性神经元特异性Smc3敲除小鼠模型，目前的研究确定了成年期Smc3消融的特异性性别依赖效应。行为测试发现Smc3基因敲除在雌性中具有抗焦虑作用，在成年基因敲除开始四周后在雄性中具有促焦虑作用。前额叶皮层是焦虑行为的调节器，在树突分支中也显示出性别依赖效应。转录分析揭示了Smc3基因敲除对雄性和雌性的基因表达影响，包括焦虑相关基因和相关转录途径的变化。虽然对焦虑行为的影响是性别特异性的，但在诱导敲除后大约10周，男性和女性都出现了自残行为。目前的研究表明，神经元SMC3以一种性别特异性的方式调节成年期的焦虑。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.