Insulin modulates mPFC gene expression and emotional behavior in a sex-specific manner following fetal growth restriction

Insulin, beyond its peripheral metabolic functions, plays a critical role in brain development and emotional regulation, particularly within the medial prefrontal cortex (mPFC). Here, we identify insulin as a mechanistic link between FR and altered behavioral responses to environmental stimuli.

Transcriptomic analyses across developmental stages using the FR rodent model reveal that peripheral insulin alters gene expression in the mPFC specifically in FR animals. Pathway analyses revealed Wnt/β-catenin signaling as a common pathway across FR and insulin conditions in both sexes, but strongly in females. Moreover, targeted insulin delivery to the mPFC modifies emotional reactivity in a sex and context-dependent manner, implicating insulin signaling in shaping long-term affective outcomes in prenatally growth-restricted animals.