A new mouse study led by UCLA Health suggests that inflammation during pregnancy can cause autism-like changes in offspring, but also suggests that these brain and behavioral effects can be rapidly but temporarily reversed in adulthood by short-term administration of the immunosuppressant rapamycin.
Even mild inflammation during the third trimester has been shown to cause autism-like symptoms in offspring, abnormal brain growth, seizures, and hypersensitivity to everyday sensory input that persists into adulthood.
In a study published in a journal nature communicationsUCLA researchers found that a single dose of the drug rapamycin significantly improved brain signaling and behavioral symptoms in these offspring within about two hours, too short a time to correct the underlying physical changes in the brain caused by maternal inflammation.
This study did not identify rapamycin as a viable treatment for these conditions in humans, given its temporary effects and potential toxicity with repeated doses. Rather, the researchers said the drug’s effects have revealed new therapeutic targets for the development of future treatments.
The level of functional normalization achieved in this short period of time suggests new mechanisms by which possible treatments may act. This suggests that the adult brain may be more adaptive than we assumed, even if fundamental structural changes from early development are still present. This points not only to the physical structure of the brain but also to its functional circuitry as a target for future therapeutic approaches. ”
Harley Kornblum, Ph.D., senior study author and director of the Center for Intellectual and Developmental Disabilities Research, Semel Institute of Neuroscience and Human Behavior, UCLA Health Sciences
Previous studies have shown that offspring of mothers who experience inflammation during pregnancy are more likely to develop autism-related traits, such as repetitive behaviors and difficulties with social interactions, as well as brain overgrowth and sensory processing deficits that persist into adulthood.
Additionally, rapamycin has been shown in previous mouse autism studies to improve symptoms by suppressing an overactive pathway that signals cell growth and proliferation, known as the mTOR pathway.
What was less clear was whether these brain changes could be corrected into adulthood and whether the benefits of rapamycin would come from long-term structural repair or from more rapid functional changes.
In this study, researchers exposed pregnant mice to a mild pro-inflammatory substance during early pregnancy. The dose was too low to cause severe symptoms in the mother. The resulting offspring developed chronic brain and body-wide inflammation, mild brain hyperproliferation, excessive cell signaling in the mTOR pathway, disorganized brain functional network connectivity and behaviors associated with autism.
When researchers gave adult children a single dose of rapamycin, they saw rapid improvement in nearly every measure. Neurons that had been firing abnormally calmed down, reducing susceptibility to seizures, brain areas that had been miscommunicating reorganized into more typical patterns, and repetitive behaviors and sensory overreactions were alleviated. These changes occurred within about two hours, a rate that cannot be explained by the physical rewiring of brain synapses, which typically takes much longer.
“These results reshape the way we treat symptoms associated with autism. If we can preserve the adult brain’s ability to normalize function, we may be able to successfully address some of the features of autism without modifying the underlying structural differences,” said lead author Dr. Janelle Le Bell, associate professor of neurosurgery at UCLA.
To understand the mechanism behind rapamycin’s rapid effects, the researchers examined gene activity in brain cells before and after treatment. Researchers found that rapamycin reversed abnormal expression of genes associated with autism, epilepsy, and ion channel function, particularly in excitable neurons, suggesting that the drug works by quickly rebalancing the excitability of brain cells rather than repairing structural differences in the brain.
The findings suggest that mTOR pathway activity, brain network organization, and neural excitability levels may be potential targets for future treatments targeting specific autism symptoms, such as sensory hypersensitivity, a common but difficult-to-treat symptom of autism.
Co-senior author Dr. Neil Harris, professor of neurosurgery at UCLA, cautioned that treatment effects were temporary and that resistance was also found to develop over several weeks when administered daily. This, along with rapamycin’s high potential toxicity and the fact that these studies were conducted in mice, makes rapamycin unsuitable for widespread use in humans.
“This points not to rapamycin itself as a treatment, but to new therapeutic targets such as neuromodulation of sensory circuits and the balance of inhibition and excitation in neurons,” Harris said.
sauce:
University of California, Los Angeles Health Sciences
Reference magazines:
Le Bell, J. Others. (2026). Acute rapamycin treatment reveals a distinct mechanism of dysfunction in a mouse model of maternal inflammation. nature communications. DOI: 10.1038/s41467-026-74958-1. https://www.nature.com/articles/s41467-026-74958-1.
