Abnormalities in a type of brain cell called astrocytes may play a central role in causing certain behavioral symptoms of autism spectrum disorders, according to a preclinical study by researchers at Weill Cornell Medicine.
For the study, published April 1 in molecular Psychiatry, The lead author Dr. Dilek Colak, an assistant professor of neuroscience at the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine, and her colleagues grew astrocytes from stem cells from autism patients and transplanted them into mice, healthy newborns. They found that after the transplant, the mice developed repetitive behaviors, a typical symptom of autism spectrum disorder (ASD), but did not develop the social deficits associated with the disease. The mice also developed memory deficits, which are commonly seen in ASD but are not a core feature of the disease.
“Our study suggests that astrocyte abnormalities may contribute to the onset and progression of autism spectrum disorders,” said Dr. Colak, who is also an assistant professor of pediatric neuroscience and a fellow at the Drukier Institute for Children’s Health. “Astrocyte abnormalities may be responsible for repetitive behaviors or memory deficits, but not for other symptoms such as difficulties in social interactions. »
Most studies on autism spectrum disorders have focused on the role of neurons, a type of brain cell that relays information around the brain. But other brain cells called astrocytes help regulate the behavior of neurons and the connections between them. Gene mutations associated with autism spectrum disorders likely affect different brain cell types differently, said Dr. cola Post-mortem studies had previously revealed astrocyte abnormalities in the brains of patients with autism spectrum disorders.
“We didn’t know if these astrocyte abnormalities contributed to disease development or if the abnormalities were a consequence of the disease,” said Dr. cola
To determine whether astrocytes might be involved early in the disease, the team obtained stem cells from patients with autism spectrum disorders, coaxed them to develop into astrocytes in the lab, and transplanted them into the brains of otherwise healthy newborn mice, resulting in a human emerged -chimera mouse.
Using a microscopic technique called two-photon imaging, they observed excessive calcium signaling in human astrocytes transplanted into mouse brains, explained co-lead author Dr.
“It was amazing to see how these human astrocytes responded to behavioral changes in active mice,” said Dr. Huang “We believe we are the first to measure the activity of human astrocytes transplanted in this way. »
To determine whether increased calcium signaling was causing the behavioral symptoms in the mice, the team infected astrocytes cultured in the laboratory from stem cells from ASD patients with a virus carrying an RNA fragment designed to reduce calcium signaling to normal levels . When they transplanted these astrocytes into mice, the animals didn’t develop memory problems.
“Future therapies for autism could capitalize on this finding by using genetic tools to limit extreme calcium swings in astrocytes,” said co-lead author Megan Allen, postdoctoral researcher in neuroscience at the Feil Family Brain and Mind Research Institute of Weill Cornell Medicine.
The findings could also have important implications for understanding and treating other neuropsychiatric disorders, such as schizophrenia, that also involve memory deficits, said Dr. cola
“It is important to determine the role of certain types of brain cells, including astrocytes, in neurodevelopmental and neuropsychiatric disorders,” she said.
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