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Social deficits via dysregulated Rac1-dependent excitability control of prefrontal cortical neurons and increased GABA/glutamate ratios.
Ma, Bingke; Shan, Xingyue; Yu, Juehua; Zhu, Tailin; Li, Ren; Lv, Hui; Cheng, Haidi; Zhang, Tiantian; Wang, Lihua; Wei, Feiyang; Meng, Bo; Yuan, Xiaobing; Mei, Bing; Zhang, Xiao-Yong; Li, Wei-Guang; Li, Fei.
Afiliación
  • Ma B; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry
  • Shan X; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry
  • Yu J; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
  • Zhu T; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
  • Li R; Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education - Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China.
  • Lv H; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
  • Cheng H; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry
  • Zhang T; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry
  • Wang L; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
  • Wei F; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
  • Meng B; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China.
  • Yuan X; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China.
  • Mei B; Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai 200062, China. Electronic address: bmei@brain.ecnu.edu.cn.
  • Zhang XY; Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education - Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai 200433, China. Electronic address: xiaoyong_
  • Li WG; Department of Rehabilitation Medicine, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: liwg@fudan.edu.cn.
  • Li F; Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education - Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,
Cell Rep ; 41(9): 111722, 2022 11 29.
Article en En | MEDLINE | ID: mdl-36450249
Identifying symptom-specific convergent mechanisms for neurodevelopmental disorders is a promising strategy in advancing therapies. Here, we show that bidirectional dysregulation of Rac1 activity in the medial prefrontal cortex (mPFC) dictates shared social deficits in mice. Selective upregulation or downregulation of Rac1 activity in glutamatergic or fast-spiking GABAergic neurons results in excessive or inadequate control of excitability combined with a decrease in glutamate or an increase in GABA concentrations and an increase in the GABA/glutamate ratio, which is responsible for social deficits. Notably, the autism model of Shank3B knockout mice exhibits aberrantly enhanced Rac1 activity, reduced glutamate concentrations, and pyramidal neuron excitability in mPFC accompanied with social deficits, which were corrected by either excitatory-neuron-specific downregulation of Rac1 activity or upregulation of neuronal excitability. Thus, this work shows a convergence between genetic autism risk factors, dysregulation of Rac1 signaling, and excitation-inhibition imbalance, enabling mechanism-based stratification of patients with social deficits.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Prefrontal / Ácido Glutámico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Corteza Prefrontal / Ácido Glutámico Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Cell Rep Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos