March 1, 2023

Social Deficits and Seizures in Autism Type Tied to Overexcited Brain Circuits 

Article published by Neuroscience News

Scientists have discovered a key feature of this subtype is a duplicated gene that results in overactive or overexcited brain circuits. The subtype is called 16p11.2 duplication syndrome.

“We found that mice with the same genetic changes found in humans are more likely to have seizures and also have social deficits,” said lead author Marc Forrest, research assistant professor of neuroscience at Northwestern University Feinberg School of Medicine.

Peter Penzes, senior author of the study, and his team also showed when they reduced the levels of a gene — PRRT2 — in the duplicated region, brain activity in mice returned to normal, normal social behavior was restored and seizures decreased.

“Our data, therefore, demonstrates that brain over-activation could be causing both seizures and social deficits in this syndrome, and that too much PRRT2 is responsible for this,” Forrest said.

The study was recently published in Nature Communications and was conducted in the laboratory of Penzes, director of the Center for Autism and Neurodevelopment and the Ruth and Evelyn Dunbar Professor of psychiatry and behavioral sciences at Northwestern.

Because the gene PRRT2 regulates how neurons talk to each other, inhibiting synapses or connection points between neurons could help treat both seizures and autism symptoms in this syndrome, Forrest said. This approach could also be used more broadly in other types of neurodevelopmental disorders with brain over-activation, which has been shown in other subtypes.

“Our work now shows that we can focus our efforts on targeting the PRRT2 pathway for novel therapies, and these could potentially cure core symptoms of 16p11.2 duplication syndrome,” Forrest said. “If we learn how the 16p11.2 duplication causes illness, maybe we can also learn more about what causes autism and schizophrenia, in general, and create better treatments.”