Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate...Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.展开更多
Autism spectrum disorders(ASD)are characterized by social and repetitive abnormalities.Although the ASD mouse model with Shank3b mutations is widely used in ASD research,the behavioral phenotype of this model has not ...Autism spectrum disorders(ASD)are characterized by social and repetitive abnormalities.Although the ASD mouse model with Shank3b mutations is widely used in ASD research,the behavioral phenotype of this model has not been fully elucidated.Here,a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice.It was found that both sexes replicated the core and accompanied symptoms of ASD,with significant sex differences.Further,Shank3b heterozygous knockout mice exhibited distinct autistic behaviors,that were significantly different from those those observed in the wild type and homozygous knockout groups.Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models,which are more clinically relevant in autistic studies.展开更多
基金supported by the Natural Science Foundation of China(32394032,82201699,and 82221001)the Natural Science Foundation of Zhejiang Province(LTGD24H250001)+1 种基金the Kay R&D Program of Shaanxi Province(2023-YBSF-093),the Young Talent Fund of University Association for Science and Technology in Shaanxi(20220306)the Joint Founding Project of Innovation Research Institute,Xijing Hospital(LHJJ24JH02).
文摘Autism Spectrum Disorder(ASD)is marked by early-onset neurodevelopmental anomalies,yet the tem-poral dynamics of genetic contributions to these processes remain insufficiently understood.This study aimed to elu-cidate the role of the Shank3 gene,known to be associated with monogenic causes of autism,in early developmental processes to inform the timing and mechanisms for poten-tial interventions for ASD.Utilizing the Shank3B knockout(KO)mouse model,we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex(ACC)across different postnatal stages.Our longitudinal analysis revealed that,while Shank3B KO mice displayed normal neuronal morphology at one week postnatal,signifi-cant impairments in dendritic growth and synaptic activity emerged by two to three weeks.These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
基金National Science and Technology Innovation 2030-Major Project of China(2021ZD0201003 and 2022ZD0208300)National Natural Science Foundation of China(32171092)+3 种基金Shenzhen Key Basic Research Project(JCYJ20220818100805013)Shenzhen Key Laboratory of Viral Vectors for Biomedicine(ZDSYS20200811142401005)Guangdong Provincial Medical Products Administration Key Laboratory of Quality Control Technology for Virus-Based Therapeutics(2020ZDB26)Guangdong Provincial Medical Products Administration(2022ZDZ13).
文摘Autism spectrum disorders(ASD)are characterized by social and repetitive abnormalities.Although the ASD mouse model with Shank3b mutations is widely used in ASD research,the behavioral phenotype of this model has not been fully elucidated.Here,a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice.It was found that both sexes replicated the core and accompanied symptoms of ASD,with significant sex differences.Further,Shank3b heterozygous knockout mice exhibited distinct autistic behaviors,that were significantly different from those those observed in the wild type and homozygous knockout groups.Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models,which are more clinically relevant in autistic studies.
基金supported by the Natural Science Foundation of Anhui Province,China(No.2408085MH189)the Scientific Research Program of University in Anhui Province,China(No.2024AH051017,KJ2021A0202)+4 种基金the Training Program for Young and Middle-aged Teachers in University of Anhui Province,China(No.YQYB2024031)the Clinical Science Research Project of the First Affiliated Hospital of Anhui University of Chinese Medicine(No.2021yfylc14)the Biomedical Basic Applied Science and Technology Public Service Platform of Large-scale Instruments and Equipment Open Fund of Anhui Province,China(No.2023-04)the Students'Innovation and Entrepreneurship Training Program of Anhui Province,China(No.S202410366078)the Scientific Research Platform and Base Upgrading Plan of Anhui Medical University(No.2021xkjT048)。
