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Insufficient myelination, likely caused by a lack of mature oligodendrocytes, is linked to autism spectrum disorder, according to a study in mice and postmortem human brains published yesterday (February 3) in Nature Neuroscience.

Myelin, the fatty substance that sheaths and insulates the axons of neurons, is responsible for aiding the quick delivery of signals throughout the brain. Too little myelin leaves the cells vulnerable to damage (as with multiple sclerosis), while too much can muddle the message. Oligodendrocytes (OL) are the cells that control myelination. Previous research has shown that myelin is typically thinner in those with autism spectrum disorder (ASD), while the current study explores the source of the problem.

While studying mouse brains for genetic mutations that cause Pitt-Hopkins syndrome, an autism-related genetic disorder, the team noticed irregular myelination and inconsistent expression of Tcf4, a gene that regulates OL activity.

Turning their attention to human cadavers, the researchers found deficiencies in myelin sheathing in brains from people with autism compared to controls, echoing what was found in the mice. A genetic analysis revealed that the homologous gene, TCF4, also contained varied mutations in regulatory regions. There was a noticeable lack of mature OL in the ASD brains when compared to the controls and an overabundance of immature cells, and myelination was not happening sufficiently.

“This makes us think that the cells that are myelinating are doing it properly, it’s just that there are not a lot of them,” coauthor Joseph Bohlen told Spectrum when his then-unpublished findings were presented at the Society for Neuroscience meeting in Chicago in October.

Future research will focus on the creation of brain organoids with irregular myelination and testing compounds that could target OL and increase myelin production. The authors’ hope is that if children with autism receive early identification, a treatment could mitigate some of their symptoms.

Lisa Winter is the social media editor for The Scientist. Email her at lwinter@the-scientist.com or connect on Twitter @Lisa831.