Chinese scientist team Cell sub-Journal publishes research results on the pathogenesis of high-functioning autism genes

On November 2, 2021, the journal "Cell Reports" published an online research paper titled "SENP1 Regulates the Core Symptoms of Autism in the Postpress Cortex"
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The research was conducted by the Chinese Academy of Sciences Brain Science and Intelligent Technology Excellence Innovation Center (Neuroscience Institute), the State Key Laboratory of Neuroscience, the Shanghai Brain Science and Brain-like Research Center Qiu Zilong Research Group, and the Li Fei team of Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai Cheng Jinke, School of Basic Medical Sciences, Jiaotong University, teamed up
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Autism is a neurodevelopmental disease that develops in infants and young children
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In recent years, the prevalence of autism in countries around the world has increased year by year, which has aroused widespread concern from all walks of life
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The core symptoms of autism are social disorders and repetitive stereotyped behaviors.
Although most children with autism are accompanied by mental retardation, some children only have the core symptoms of autism and their intellectual development is normal, which is also called high functioning.
Children with autism
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At present, there is a lack of research on whether there are genetic genes and neural circuits specific to the core symptoms of autism in high-functioning autism
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************************************************** ************* In an all-exome second-generation sequencing project for more than 700 core families with autism, Qiu Zilong’s research team found that one has a high developmental quotient and lacks intelligence Autistic children with developmental delay
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The child only carries a heterozygous new mutation (de novo mutation) in the Sentrin-specific peptidase 1 (SENP1) gene, which causes the child's SENP1 gene to be half-dose under-dose
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The molecular mechanism of SENP1 gene mutations causing autism has not yet been reported
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The research team combined a variety of animal behavior experiments and found that Senp1 heterozygous mice have the core symptoms of autism with social memory impairment and repetitive stereotyped behaviors, but they do not have symptoms such as cognitive impairment and spatial memory impairment
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Using techniques such as brain slice immunofluorescence staining and patch-clamp electrophysiological recording, the research team found that Senp1 heterozygous mice had an increase in the number of GABAergic interneurons and pyramidal neurons in the retrosplenial agranular cortex (RSA).
Phenotypes such as increased inhibitory synapses and decreased excitatory synapses (Figure 1)
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This suggests that the RSA brain area has a potentially important influence on the core symptoms of autism
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Further studies have shown that SENP1 mediates fragile X mental retardation protein (FMRP) dehaematization through dehaematization enzyme activity, thereby regulating the expression of FMRP at the postsynapse, thereby affecting excitability and inhibitory synapse formation
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The research team used virus stereotactic injection technology combined with animal behavior experiments and found that replenishing SENP1 protein or FMRP protein in the RSA brain area can effectively improve the core symptoms of autism in Senp1 heterozygous mice
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This study reported for the first time that SENP1, as a new autism risk gene, regulates the molecular mechanism of core symptoms of autism in the RSA brain region, providing important evidence for in-depth understanding of the genetic basis of mammalian social behavior, and for further intervention and improvement of autism The core symptoms provide new ideas
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Figure 1: The molecular mechanism by which SENP1 regulates FMRP desmatization and affects the core symptoms of autism
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The half-time under-dose effect of SENP1 leads to excessive hematoxylation and excessive degradation of FMRP
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The down-regulation of FMRP expression in inhibitory and excitatory postsynapses will lead to an increase in inhibitory synapses and a decrease in excitatory synapses
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Disorders of excitatory-inhibitory synaptic connections in the RSA brain area will further cause the RSA brain area to fail to properly integrate sensory signals, which will eventually cause the core symptoms of autism
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Figure 2: This Chinese painting abstractly summarizes the main phenotypes of SENP1 that regulate the core symptoms of autism in the post-compression cortex
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SENP1 half-time under-dose effect (the winter plum tree trunk is split in half) leads to an increase in the number of immature dendritic spines (unopened winter plum buds) and mature dendritic spines (open winter plum) in the cortex (Chinese->
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These phenotypes are associated with impaired social memory (kittens have no social interaction with their partners)
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(This painting was created by Yang Kan, the co-first author and co-corresponding author of the paper, and Qiu Yongzhi, a young painter
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) The research is mainly composed of assistant researcher Yang Kan, postdoctoral fellow at the Center for Excellence in Brain Intelligence, Chinese Academy of Sciences, Shi Yuhan, postdoctoral fellow, and doctoral student Du at Xinhua Hospital affiliated to Shanghai Jiaotong University.
Xiujuan cooperation is completed
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This research has received important guidance from researcher Xu Huatai from the Center for Excellence in Brain Intelligence of the Chinese Academy of Sciences and Professor Yu Juehua from Kunming Medical University
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Zhang Yuefang, Shan Shifang, Yuan Yiting, Fan Liu, PhD students Wang Jincheng, Wang Ruoqing, Zhou Chenhuan, and Wang Yanzhi from the Center of Excellence for Brain Intelligence of the Chinese Academy of Sciences, and Liu Yuting and Cai Zilin, undergraduates of Shanghai Jiaotong University College of Science and Technology, participated in this research
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The research also received strong support from the optical platform of the Chinese Academy of Sciences Brain Intelligence Center of Excellence and Dr.
Hu Qian, experimental animal platform, electron microscope technology platform, gene editing platform and molecular cell technology platform
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The research was jointly funded by the Chinese Academy of Sciences, the Ministry of Science and Technology, the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission and the China Postdoctoral Fund
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Link to the paper: https:// 2020 Hot Article Selection 1.
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