Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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
_version_ 1784569244798681088
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
work_keys_str_mv AT lopezarandamanuelf postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT chattopadhyayishanu postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT boxxgaylem postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT fraleyelizabethr postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT silvatawniek postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT zhoumiou postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT phanmiranda postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT herreraisaiah postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT talomasunrae postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT mandanasrochelle postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT bachkaren postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT gandalmichael postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT geschwinddanielh postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT chenggenhong postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT rzhetskyandrey postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT whitestephaniea postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications
AT silvaalcinoj postnatalimmuneactivationcausessocialdeficitsinamousemodeloftuberoussclerosisroleofmicrogliaandclinicalimplications