Inflammation in supporting brain cells called astrocytes may contribute to neuronal dysfunction in at least some subtypes of autism spectrum disorder (ASD), according to a new study led by researchers at the University of California San Diego School of Medicine. Importantly, the research suggests that this neuronal damage might be reversible through novel anti-inflammatory therapies.
The research involved dental pulp cells donated from the baby teeth of three children with diagnoses of non-syndromic autism (part of the on-going Tooth Fairy Project). The researchers reprogrammed these cells to become either neurons or astrocytes, a type of glia or support cell abundantly found in the brain. The cells were grown into organoids, which are essentially mini-brains in a dish.
Though genetically distinct, all three children exhibited stereotypical ASD behaviors, such as lack of verbal skills or social interaction. When the scientists analyzed the developed organoids in microscopic detail, they found that the neurons had fewer synapses (connections to other neurons) and other network defects. Additionally, some astrocytes showed high levels of interleukin 6 (IL-6), a pro-inflammatory protein. High levels of IL-6 are toxic to neurons.
The researchers then co-cultured astrocytes derived from the ASD children with neurons taken from healthy controls. The healthy neurons behaved like ASD neurons, said co-senior author Alysson R. Muotri, Ph.D., professor in the University of California San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the University of California San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.
“But more importantly, the opposite was true. When we co-cultured ASD neurons with normal astrocytes, we could rescue the cellular defects. The neurons reverted to normal functioning and behavior,” said Muotri.
The researchers say the data suggests there may be an intrinsic inflammatory reaction within a subgroup of persons with ASD.
“What we are trying to do now is understand if we can predict this subgroup through genome sequencing and, perhaps, find a therapeutic opportunity to treat them with anti-inflammatory drugs.”
The findings are published in the journal Biological Psychiatry.