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社会环境对野生型和自闭症小鼠模型嗅觉和社交技能的影响。

Effect of the social environment on olfaction and social skills in wild-type and a mouse model of autism.

机构信息

INRAE, CNRS, Université de Tours, PRC, Nouzilly, France.

LE STUDIUM Loire Valley Institute for Advanced Studies, Orléans, France.

出版信息

Transl Psychiatry. 2024 Nov 7;14(1):464. doi: 10.1038/s41398-024-03174-6.

Abstract

Autism spectrum disorders (ASD) are complex, polygenic and heterogenous neurodevelopmental conditions. The severity of autism-associated variants is influenced by environmental factors, particularly social experiences during the critical neurodevelopmental period. While early behavioral interventions have shown efficacy in some children with autism, pharmacological support for core features - impairments in social interaction and communication, and stereotyped or restricted behaviors - is currently lacking. In this study, we examined how the social environment influences both wild-type (WT) and Shank3 knockout (KO) mice, a model reflecting core autism-like traits. Our findings revealed that chronic social isolation enhanced social interaction and olfactory neuron responses in WT animals. Furthermore, it restored impairments in social novelty preference and olfactory function, as well as self-grooming in Shank3 KO mice. Conversely, an enriched social environment heightened social interest toward novel conspecifics in WT mice, but elicited the opposite effect in Shank3 KO mice. Notably, Shank3 KO mice displayed distinct social responses when exposed to WT or Shank3 KO mice. These results offer novel insights that could favor the implementation of behavioral interventions and inclusive classroom programs for children with ASD.

摘要

自闭症谱系障碍(ASD)是一种复杂的、多基因的、异质的神经发育障碍。自闭症相关变异的严重程度受环境因素影响,特别是在关键神经发育期间的社会经历。虽然早期行为干预在一些自闭症儿童中已显示出疗效,但目前缺乏针对社交互动和沟通受损以及刻板或受限行为等核心特征的药物支持。在这项研究中,我们研究了社会环境如何影响野生型(WT)和 Shank3 敲除(KO)小鼠,这一模型反映了核心自闭症样特征。我们的研究结果表明,慢性社会隔离增强了 WT 动物的社交互动和嗅觉神经元反应。此外,它恢复了 Shank3 KO 小鼠在社交新颖性偏好和嗅觉功能以及自我修饰方面的缺陷。相反,丰富的社会环境增强了 WT 小鼠对新同类的社交兴趣,但在 Shank3 KO 小鼠中产生了相反的效果。值得注意的是,Shank3 KO 小鼠在接触 WT 或 Shank3 KO 小鼠时表现出不同的社交反应。这些结果提供了新的见解,可能有利于为 ASD 儿童实施行为干预和包容课堂计划。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a42/11542099/fce94c8f3092/41398_2024_3174_Fig1_HTML.jpg

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