Rapamycin Reverses ASD-Like Behaviors in 2 Hours in Maternal-Inflammation Mice
Updated
Updated · Nature.com · Jul 23
Rapamycin Reverses ASD-Like Behaviors in 2 Hours in Maternal-Inflammation Mice
3 articles · Updated · Nature.com · Jul 23
Summary
A single rapamycin dose normalized repetitive behavior, sensory over-responsivity, social deficits, neuronal hyperexcitability and seizure susceptibility in adult mice exposed to maternal inflammation in utero, with effects appearing within 2 hours.
Brain mTOR inhibition—not reduced systemic inflammation—appeared to drive the rescue: rapamycin rapidly lowered phospho-S6, restored excitatory-inhibitory balance, and reversed abnormal sensory-thalamic functional connectivity and network modularity.
The maternal-inflammation model showed persistent ASD-linked features across adulthood, including chronic cytokine elevation, brain overgrowth followed by regional volume shifts, sensory dysregulation and heightened seizure risk.
The benefit was temporary, with repetitive behaviors returning by 72 hours after one dose and efficacy fading during 5 weeks of daily treatment, suggesting rapamycin itself is a mechanistic probe rather than a broad long-term therapy.
The findings point to mTOR-related sensory-circuit dysfunction, ion-channel regulation and network organization as potential treatment targets for core and comorbid autism phenotypes.