A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2023 | Number 2, Volume 36

Abnormalities of astrocytes again implicated in autism

A new study adds to evidence that abnormalities in star-shaped cells called astrocytes, which provide support for neurons in the brain and central nervous system, may play a role in autism spectrum disorders (ASD). 

In the study, Megan Allen and colleagues grew astrocytes from stem cells derived from individuals with ASD and transplanted them into the brains of newborn mice. The researchers found that following the transplants, the mice developed repetitive behaviors—a hallmark of autism spectrum disorders (ASD)—and exhibited memory deficits. However, the mice did not develop the social deficits associated with the disease. 

Study coauthor Dilek Colak says, “Our study suggests that astrocyte abnormalities might contribute to the onset and progression of autism spectrum disorders. Astrocyte abnormalities may be responsible for repetitive behavior or memory deficits, but not other symptoms like difficulties with social interactions.” 

The researchers also found that the transplanted human astrocytes in the brains of the mice exhibited excessive calcium signaling. To determine if this increased calcium signaling was causing the mice’s behavioral symptoms, the team infected astrocytes grown from the stem cells of individuals with ASD with a virus carrying a fragment of RNA designed to reduce calcium signaling to normal levels. When the researchers transplanted these astrocytes into the mice, the animals did not develop memory problems.

Allen comments, “Future therapies for autism might exploit this finding by using genetic tools to limit extreme calcium fluctuations inside astrocytes.” The new study adds to evidence that astrocytes play a role in autism. In a previous study, (see ARRI 2017, No. 4), Fabiele Baldino Russo and colleagues took dental pulp cells from the baby teeth of three children with non-syndromic autism spectrum disorders (ASD)—that is, ASD not due to any known cause—and reprogrammed the cells to become either neurons or astrocytes. 

The researchers then grew the cells into organoids, or “mini-brains.” Examining these organoids microscopically, the researchers found that the neurons had structural defects and that some of the astrocytes had high levels of a pro-inflammatory protein called interleukin 6 (IL-6), which is toxic to neurons. 

When Russo and colleagues combined astrocytes from the dental pulp of children with ASD with neurons from neurotypical controls and cultured them, they found that the neurons from the controls behaved like the neurons from the children with ASD. “But more importantly,” according to study coauthor Alysson Muotri, “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.”


Citations

“Astrocytes derived from ASD individuals alter behavior and destabilize neuronal activity through aberrant Ca2+ signaling,” Megan Allen, Ben S. Huang, Michael J. Notaras, Aiman Lodhi, Estibaliz Barrio-Alonso, Pablo J. Lituma, Paul Wolujewicz, Jonathan Witztum, Francesco Longo, Maoshan Chen, David W. Greening, Eric Klann, M. Elizabeth Ross, Conor Liston, and Dilek Colak, Molecular Psychiatry, April 1, 2022 (free online). Address: Dilek Colak, [email protected]

—and— 

“Some autism spectrum disorder symptoms linked to astrocytes,” news release, Weill Cornell Medicine, April 21, 2022. 

—and— 

“Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells,” Fabiele Baldino Russo, Beatriz Camille Freitas, Graciela Conceição Pignatari, Isabella Rodrigues Fernandes, Jonathan Sebat, Alysson Renato Muotri, and Patricia Cristina Baleeiro Beltrão-Braga, Biological Psychiatry, October 3, 2017 (online). Address: Patricia Cristina Baleeiro Beltrão-Braga, Av. Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, 05508-270. São Paulo, SP. Brazil. [email protected]

—and— 

“Inflamed support cells appear to contribute to some kinds of autism,” Scott LaFee, UC San Diego Health, October 18, 2017.