Journal Club (January 17, 2021)


Inflammation stresses out brain development


Nature Neuroscience volume 24, pages155–157(2021)

Published: 23 December 2020
Maternal immune activation in mice disrupts proteostasis in the fetal brain

Brian T. Kalish, Eunha Kim, Benjamin Finander, Erin E. Duffy, Hyunju Kim, Casey K. Gilman, Yeong Shin Yim, Lilin Tong, Randal J. Kaufman, Eric C. Griffith, Gloria B. Choi, Michael E. Greenberg & Jun R. Huh
Nature Neuroscience volume 24, pages204–213(2021


Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.


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