Nature communicationsJul 23, 2026

Short-term rapamycin treatment shows different ways inflammation during pregnancy causes problems in mice

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Updated Jul 25, 2026

Abstract

Within 2 hours, rapamycin rescues neuronal hyperexcitability and seizure susceptibility in adult mice exposed to maternal inflammatory response.

Maternal inflammatory response during early gestation is linked to physiological and behavioral changes associated with autism spectrum disorder.
Mild maternal inflammation causes chronic inflammation in both the body and brain, activating the mTOR pathway.
Acute treatment with rapamycin leads to improvements in functional network connectivity and sensory processing in adult offspring.
Altered gene expression related to autism, ion channels, and epilepsy is observed following maternal inflammation.
mTOR dysregulation is indicated as a driver of dysfunctional brain development in offspring of mothers with inflammation.

Simplified

Maternal inflammatory response (MIR) during early mouse gestation induces a cascade of physiological and behavioral changes associated with autism spectrum disorder (ASD). We have shown that mild MIR causes chronic systemic and brain inflammation, mTOR pathway activation, mild brain overgrowth with regionally specific volumetric changes, sensory processing dysregulation, and repetitive behavior abnormalities. Prior rapamycin studies in autism models focused on chronic treatments that alter or prevent physical brain changes. Here, we focus on acute rapamycin effects to uncover novel mTOR pathway-mediated mechanisms of dysfunction. Within 2 hours, rapamycin rescues neuronal hyperexcitability, seizure susceptibility, functional network connectivity, brain community structure, repetitive behaviors, and sensory over-responsivity in adult MIR offspring. These CNS-mediated effects coincide with altered expression of genes associated with ASD, ion channels, and epilepsy. Our findings demonstrate that mTOR dysregulation drives dysfunctional brain development in MIR offspring but the adult brain remains amenable to rapid functional normalization, rescuing core and comorbid ASD-associated brain and behavior phenotypes. Restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing multiple ASD phenotypes.

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Short-term rapamycin treatment shows different ways inflammation during pregnancy causes problems in mice

Abstract

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