PT  - JOURNAL ARTICLE
AU  - Evan A Bordt
AU  - Haley A Moya
AU  - Young Chan Jo
AU  - Caitlin T. Ravichandran
AU  - Izabella M. Bankowski
AU  - Alexis M. Ceasrine
AU  - Christopher J McDougle
AU  - William A. Carlezon, Jr
AU  - Staci D Bilbo
TI  - Gonadal Hormones Impart Male-Biased Behavioral Vulnerabilities to Immune Activation via Microglial Mitochondrial Function
AID  - 10.1101/2022.08.05.502953
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.05.502953
4099  - http://biorxiv.org/content/early/2022/08/06/2022.08.05.502953.short
4100  - http://biorxiv.org/content/early/2022/08/06/2022.08.05.502953.full
AB  - There is a strong male bias in the prevalence of many neurodevelopmental disorders such as autism spectrum disorder. However, the mechanisms underlying this sex bias remain elusive. Infection during the perinatal period is associated with an increased risk of neurodevelopmental disorder development. Here, we used a mouse model of early-life immune activation that reliably induces deficits in social behaviors only in males. We demonstrate that male-biased alterations in social behavior are dependent upon microglial immune signaling and are coupled to alterations in mitochondrial morphology, gene expression, and function specifically within microglia, the innate immune cells of the brain. Additionally, we show that this behavioral and microglial mitochondrial vulnerability to early-life immune activation is programmed by the male-typical perinatal gonadal hormone surge. These findings demonstrate that social behavior in males over the lifespan are regulated by microglia-specific mechanisms that are shaped by events that occur in early development.Competing Interest StatementDr. McDougle serves as a consultant to Precidiag, Receptor Life Sciences, Sage Therapeutics and Acadia Pharmaceuticals. He receives royalties from Oxford University Press and Springer Publishing.