Centers and Institutes
Published September 17, 2021 | Version v1
Journal article Open

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

Creators

  • 1. University of California, Los Angeles
  • 2. University of Chicago

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.

Data availability

PLX5622 was obtained under a material transfer agreement with Plexxikon. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.

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sciadv.abf2073.pdf

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Additional details

Identifiers

DOI
10.1126/sciadv.abf2073
Other
oai:uchicago.tind.io:11071

Funding

Children's Tumor Foundation
2014-01-014
Human Frontier Science Program
LT000822/2011-L
National Institute of Mental Health
R01 MH084315
Takeda Pharmaceutical Company Limited

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Human Genetics, Medicine
Center(s) or Institute(s)
Institute for Genomics and Systems Biology