2026-06-01T02:44:27Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/392542026-02-03T11:15:32Zcom_10630_2254col_10630_37953

Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: role of microglia and clinical implications López-Aranda, Manuel Francisco Chattopadhyay, Ishanu Boxx, Gayle M. Fraley, Elizabeth R. Silva, Tawnie K. Zhou, Miou Phan, Miranda Herrera, Isaiah Taloma, Sunrae Mandanas, Rochelle Bach, Karen Gandal, Michael Geschwind, Daniel H. Cheng, Genhong Rzhetsky, Andrey White, Stephanie A. Silva, Alcino J. Esclerosis tuberosa - Modelos animales Microglia - Investigación Trastornos del espectro autista This work was supported by the Human Frontier Science Program (reference no. LT000822/2011-L), Children’s Tumor Foundation (grant no. 2014-01-014), Takeda Pharmaceutical Company Limited, and NIH R01 MH084315 to A.J.S. 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. 2025-07-08T07:08:42Z 2025-07-08T07:08:42Z 2021-09-17 journal article López-Aranda MF, Chattopadhyay I, Boxx GM, Fraley ER, Silva TK, Zhou M, Phan M, Herrera I, Taloma S, Mandanas R, Bach K, Gandal M, Geschwind DH, Cheng G, Rzhetsky A, White SA, Silva AJ. Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications. Sci Adv. 2021 Sep 17;7(38):eabf2073. doi: 10.1126/sciadv.abf2073. Epub 2021 Sep 17. PMID: 34533985; PMCID: PMC8448451. https://hdl.handle.net/10630/39254 10.1126/sciadv.abf2073 eng http://creativecommons.org/licenses/by-nc/4.0/ open access Attribution-NonCommercial 4.0 Internacional AAAS