RT Journal Article
T1 Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: role of microglia and clinical implications
A1 López-Aranda, Manuel Francisco
A1 Chattopadhyay, Ishanu
A1 Boxx, Gayle M.
A1 Fraley, Elizabeth R.
A1 Silva, Tawnie K.
A1 Zhou, Miou
A1 Phan, Miranda
A1 Herrera, Isaiah
A1 Taloma, Sunrae
A1 Mandanas, Rochelle
A1 Bach, Karen
A1 Gandal, Michael
A1 Geschwind, Daniel H.
A1 Cheng, Genhong
A1 Rzhetsky, Andrey
A1 White, Stephanie A.
A1 Silva, Alcino J.
K1 Esclerosis tuberosa - Modelos animales
K1 Microglia - Investigación
K1 Trastornos del espectro autista
AB 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.
PB AAAS
YR 2021
FD 2021-09-17
LK https://hdl.handle.net/10630/39254
UL https://hdl.handle.net/10630/39254
LA eng
NO 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.
NO 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.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026