Researchers at Columbia and Vanderbilt universities have made an important discovery in mice that has implications for understanding the gastrointestinal (GI) problems experienced by some children with autism.
Their findings, published Monday in the Journal of Clinical Investigation, focused on the serotonin transporter (SERT), which regulates the supply of the neurotransmitter serotonin in the brain, and which also plays a role in normal development of the gut.
Researchers at Columbia University Medical Center led by Kara Gross Margolis, M.D., and Michael Gershon, M.D., studied a strain of mice produced at Vanderbilt that had the most common mutation of the SERT gene seen in children with autism spectrum disorder (ASD).
These mice not only exhibited repetitive behaviors and social withdrawal suggestive of ASD, but also GI disturbances, particularly constipation.
The mutation induces a state of hyperactivity in SERT, causing excessive serotonin inactivation. In addition to exhibiting behaviors suggestive of autism, the researchers found that the enteric nervous system, which governs the function of the gut, also did not develop normally in these mice.
“This is the first evidence that alterations in a specific neurotransmitter system linked to autism may also contribute to the subject’s GI disturbances,” said Randy Blakely, Ph.D., whose lab at Vanderbilt University Medical Center generated the mouse model.
“This is a big step forward linking other medical issues (in autism) with the behavioral,” he said.
Prucalopride is a drug developed to treat chronic constipation that replaces the serotonin signal lost due to excessive inactivation by SERT. When the researchers gave it to pregnant mice with the SERT mutation, it prevented development of gastrointestinal disturbances in their offspring.
While this suggests the drug may prevent gastrointestinal problems in some children with autism, “we still need to learn if we can reverse these changes once they appear,” Margolis said in a news release.
Jeremy Veenstra-VanderWeele, M.D., a former Vanderbilt faculty member who now is at Columbia, contributed to the research.
