Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications.

Autor: López-Aranda MF; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Chattopadhyay I; Department of Medicine and Human Genetics, Section of Computational Biomedicine and Biomedical Data Science, and Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.; Department of Medicine, University of Chicago, Chicago, IL, USA., Boxx GM; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Fraley ER; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA., Silva TK; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Zhou M; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Phan M; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Herrera I; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Taloma S; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Mandanas R; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Bach K; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA., Gandal M; Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Geschwind DH; Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA., Cheng G; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA., Rzhetsky A; Department of Medicine and Human Genetics, Section of Computational Biomedicine and Biomedical Data Science, and Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.; Department of Medicine, University of Chicago, Chicago, IL, USA.; Department of Human Genetics, University of Chicago, Chicago, IL, USA., White SA; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA., Silva AJ; Departments of Neurobiology, Psychology, and Psychiatry, Integrative Center for Learning and Memory, and Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Sep 17; Vol. 7 (38), pp. eabf2073. Date of Electronic Publication: 2021 Sep 17.
DOI: 10.1126/sciadv.abf2073
Abstrakt: There is growing evidence that prenatal immune activation contributes to neuropsychiatric disorders. Here, we show that early postnatal immune activation resulted in profound impairments in social behavior, including in social memory in adult male mice heterozygous for a gene responsible for tuberous sclerosis complex ( Tsc2 +/− ), a genetic disorder with high prevalence of autism. Early postnatal immune activation did not affect either wild-type or female Tsc2 +/− mice. We demonstrate that these memory deficits are caused by abnormal mammalian target of rapamycin–dependent interferon signaling and impairments in microglia function. By mining the medical records of more than 3 million children followed from birth, we show that the prevalence of hospitalizations due to infections in males (but not in females) is associated with future development of autism spectrum disorders (ASD). Together, our results suggest the importance of synergistic interactions between strong early postnatal immune activation and mutations associated with ASD.
Databáze: MEDLINE