A UCLA Health study in mice has found that inflammation during pregnancy can produce lasting autism-like changes in offspring. The researchers also found that many of the resulting brain and behavioral effects could be rapidly improved in adulthood, although only temporarily, with a single dose of the immunosuppressant drug rapamycin.
Previous research has shown that even mild inflammation in the middle of pregnancy can affect the development of offspring. Reported consequences include autism-like behaviors, unusual brain growth, seizures, and increased sensitivity to sounds, touch, and other common sensory experiences. These effects can continue into adulthood.
In the new study, published in Nature CommunicationsUCLA scientists found that one dose of rapamycin improved brain communication and behavior in affected mice within about two hours. That response was too rapid for the drug to have repaired the underlying physical changes in the brain caused by maternal inflammation.
A rapid but temporary brain response
The researchers stressed that rapamycin should not be considered a practical treatment for these symptoms in people. Its benefits were temporary, repeated use can be toxic, and the study was conducted in mice. Instead, the rapid response helped reveal biological processes that could guide the development of safer and more specific therapies.
“The level of functional normalization achieved in this short time suggests new mechanisms by which potential treatments may act,” said the study’s lead author, Dr. Harley Kornblum, director of the UCLA Intellectual and Developmental Disabilities Research Center at the Semel Institute for Neuroscience and Human Behavior. “This suggests that the adult brain may be more adaptive than we assume, even when the underlying structural changes from early development are still there. This points us to the brain’s functional circuits, not just its physical structure, as a target for future treatment approaches.”
Previous studies have found that children born to mothers who experience inflammation during pregnancy may have a higher chance of developing traits associated with autism. These may include repetitive behavior, challenges with social interaction, enlarged brain growth, and altered sensory processing that persists later in life.
Rapamycin has also produced improvements in previous autism studies in mice. The drug works in part by reducing the activity of the mTOR pathway, a biological signaling system that regulates cell growth and proliferation. Excessive mTOR activity has been linked to some autism-related conditions.
However, scientists did not know whether the brain effects caused by maternal inflammation could still be modified in adulthood. It was also unclear whether rapamycin worked by gradually repairing brain structure or by producing more rapid changes in the functioning of brain circuits.
Modeling inflammation during pregnancy
To investigate, the researchers exposed pregnant mice to a mild inflammatory stimulus early in pregnancy. The dose was low enough that the mothers did not become significantly ill.
Their descendants subsequently developed persistent inflammation in both the brain and the rest of the body. They also showed mild overgrowth of the brain, excessive signaling through the mTOR pathway, poorly organized communication through functional brain networks, and behaviors associated with autism.
The researchers then gave the adult offspring a single dose of rapamycin. Improvements appeared in almost every measure they examined.
Neurons that had been unusually active began to fire more normally. The animals became less vulnerable to seizures. Brain regions that had not communicated adequately shifted toward more typical patterns. Repetitive behaviors, sensory sensitivity, and excessive responses to sensory stimuli also decreased.
All of these changes emerged in about two hours. Because physical remodeling of brain synapses generally takes longer, the scientists concluded that rapamycin was changing brain function rather than rebuilding the brain’s underlying structure.
“These results rethink how symptoms associated with autism might be treated. If the adult brain remains capable of functional normalization, then some features of autism can be successfully addressed without needing to correct underlying structural differences,” said the paper’s first author, Dr. Janel Le Belle, an associate professor in the UCLA Department of Neurosurgery.
Neural activity rebalanced with rapamycin
To determine how the drug worked so quickly, the team analyzed gene activity in brain cells before and after treatment.
Rapamycin reversed abnormal gene expression patterns linked to autism, epilepsy, and ion channel function. The strongest effects appeared in excitatory neurons, which stimulate activity in brain networks.
This suggests that the drug quickly restored a healthier balance in neuronal excitability rather than repairing structural differences formed during early development.
The results point to several possible targets for future treatments, including the activity of the mTOR pathway, the organization of brain networks, and the balance of excitation between neurons. These approaches could address specific symptoms of autism, including sensory overresponsiveness, which is common and often difficult to treat.
Why rapamycin is not the treatment
Dr. Neil Harris, co-senior author and professor in the UCLA Department of Neurosurgery, cautioned that the benefits did not last. The researchers also found that the daily treatment became less effective after several weeks as the mice developed tolerance.
Those limitations, combined with rapamycin’s potential toxicity and the fact that the findings come from animal experiments, make the drug unsuitable for widespread use in humans.
“This points toward new therapeutic targets such as neuromodulation of the sensory circuit or balancing neuronal inhibition and excitation, rather than rapamycin itself as a treatment,” Harris said.
Key takeaways
- In mice, inflammation during pregnancy caused lasting autism-like changes in brain activity and behavior, indicating that early immune disruption can influence brain development well into adulthood.
- One dose of rapamycin rapidly improved brain hyperactivity, susceptibility to seizures, sensory sensitivity, repetitive behavior, and abnormal communication between brain networks.
- The rapid response suggests that some functional changes related to autism may remain modifiable into adulthood, even when physical differences in brain structure are still present.
- The effects of rapamycin were temporary and repeated treatment became less effective. Its toxicity and the nature of animal-based research mean it is unlikely to become a widely used treatment, but the findings may help scientists identify safer therapeutic targets.