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Post-Natal Immune Activation Causes Social Deficits in a Mouse Model of Tuberous Sclerosis: Role of Microglia and Clinical Implications

EVENT: 
Weekly Seminar | Not Open to the Public
Who Should Attend: 
Researchers

Speakers

Dr. Alcino Silva's Photo
UCLA Distinguished Professor
Departments of Neurobiology, Psychiatry & Biobehavioral Sciences, and Psychology

Abstract

There is growing evidence that pre-natal immune activation contributes to neuropsychiatric disorders. We will show that early post-natal 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. Interestingly, early post-natal immune activation did not affect either wild type (WT) or female Tsc2+/- mice. We demonstrate that these memory deficits are caused by abnormal mammalian target of rapamycin (mTOR)-dependent interferon signaling and impairments in microglia function. By mining the medical records of over 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 autistic spectrum disorders (ASD). Altogether, our results suggest the importance of synergistic interactions between strong early post-natal immune activation and mutations in ASD.

Dr. Alcino Silva's Figure

Publications

Mary T Joy, Einor Ben Assayag, Dalia Shabashov-Stone, Sigal Liraz-Zaltsman, Jose Mazzitelli, Marcela Arenas, Nora Abduljawad, Efrat Kliper, Amos D Korczyn, Nikita S Thareja, Efrat L Kesner, Miou Zhou, Shan Huang, Tawnie K Silva, Noomi Katz, Natan M Bornstein, Alcino J Silva, Esther Shohami, S Thomas Carmichael
CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury
Cell . 2019 Feb 21;176(5):1143-1157.e13. doi: 10.1016/j.cell.2019.01.044.
James R Howe 6th, Mark F Bear, Peyman Golshani, Eric Klann, Stuart A Lipton, Lennart Mucke, Mustafa Sahin, Alcino J Silva
The mouse as a model for neuropsychiatric drug development
Curr Biol . 2018 Sep 10;28(17):R909-R914. doi: 10.1016/j.cub.2018.07.046.
Adam C Frank, Shan Huang, Miou Zhou, Amos Gdalyahu, George Kastellakis, Tawnie K Silva, Elaine Lu, Ximiao Wen, Panayiota Poirazi, Joshua T Trachtenberg, Alcino J Silva
Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory
Nat Commun . 2018 Jan 29;9(1):422. doi: 10.1038/s41467-017-02751-2.

When

Tuesday, November 17, 2020 - 12:30pm

Where

Conference Room: 
Online Webinar

More Information

Darlene White