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Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications
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 tuberou...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448451/ https://www.ncbi.nlm.nih.gov/pubmed/34533985 http://dx.doi.org/10.1126/sciadv.abf2073 |
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author | López-Aranda, Manuel F. 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. |
author_facet | López-Aranda, Manuel F. 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. |
author_sort | López-Aranda, Manuel F. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8448451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-84484512021-09-27 Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications López-Aranda, Manuel F. 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. Sci Adv Neuroscience 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. American Association for the Advancement of Science 2021-09-17 /pmc/articles/PMC8448451/ /pubmed/34533985 http://dx.doi.org/10.1126/sciadv.abf2073 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Neuroscience López-Aranda, Manuel F. 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. Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title | Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title_full | Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title_fullStr | Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title_full_unstemmed | Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title_short | Postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: Role of microglia and clinical implications |
title_sort | postnatal immune activation causes social deficits in a mouse model of tuberous sclerosis: role of microglia and clinical implications |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448451/ https://www.ncbi.nlm.nih.gov/pubmed/34533985 http://dx.doi.org/10.1126/sciadv.abf2073 |
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