A new study has revealed that inflammation during pregnancy may lead to changes in the brain and behavior of offspring that resemble some features of autism spectrum disorder.
However, it also showed that these changes may be temporarily reversible during adulthood using a single dose of rapamycin (an immunosuppressant drug that has been used medically for years, especially to prevent the body from rejecting transplanted organs such as kidneys after transplantation).
The study was conducted by researchers from the University of California, Los Angeles (UCLA) Health Center, who found that exposure of pregnant mice to mild inflammation during mid-pregnancy led to disorders in their offspring, including repetitive behaviors, difficulties in interaction, hypersensitivity to sensory stimuli, abnormal brain development, and an increased likelihood of epileptic seizures.
The researchers showed that giving a single dose of rapamycin to adult mice resulted in a marked improvement in brain activity and behavior in just about two hours.
They explained that the speed of improvement indicates that the drug does not work by rebuilding neural connections or changing brain structure, but rather by modifying the functions of nerve cells and regulating the activity of brain circuits.
Dr. Harley Kornblum, lead author of the study and director of the Center for Intellectual and Developmental Disabilities Research at the Semel Institute for Neuroscience and Human Behaviour at UCLA, said the findings suggest that the adult brain may have a greater capacity to adapt and recover some functions than previously thought, even when changes have arisen during early stages of development.
He added that these findings direct researchers towards targeting brain functions and neural circuits, and not just focusing on structural differences.
The study was based on a finding from previous research linking maternal inflammation during pregnancy to an increased likelihood of autism-related traits in offspring. Other studies have also indicated that rapamycin may improve some of these symptoms in mice by inhibiting mTOR, a cellular pathway that regulates growth and activity within cells.
In the new experiment, researchers found that offspring of mice exposed to inflammation showed excessive activity in the mTOR pathway and disruption in communication between brain regions, along with the emergence of autism-related behaviors.
After administering a single dose of rapamycin, the research team observed a decrease in abnormal nerve cell activity, improved communication between brain regions, and a reduction in repetitive behaviors and sensory overreaction.
Dr. Janelle Le Bell, associate professor in the Department of Neurosurgery at UCLA and lead author of the study, said the findings could open the door to new ways of treating some of the symptoms associated with autism, by improving brain function even without changing the underlying structural differences.
Gene activity analyses also showed that rapamycin helped to reorganize gene patterns associated with autism, epilepsy, and neuronal function, supporting the idea that its effect is related to restoring balance in brain activity.
Despite the promising results, the researchers stressed that rapamycin is not currently a treatment for autism in humans, as its effect was temporary, and its long-term use may lead to side effects due to its immunosuppressive effect.
Dr. Neil Harris, the study's lead co-author, pointed out that the importance of the research lies not in using rapamycin itself as a treatment, but in uncovering new therapeutic targets, such as regulating brain circuits and achieving a better balance between nerve cell activity, with the aim of developing safer and more effective future treatments.
The study's findings were published in the journal Nature Communications.
