Some autism spectrum disorder symptoms linked to astrocytes

Date:
April 21, 2022
Source:
Weill Cornell Medicine
Summary:
Abnormalities in a type of brain cell called astrocytes may play a
pivotal role in causing some behavioral symptoms of autism spectrum
disorders, according to a preclinical study.



FULL STORY ========================================================================== Abnormalities in a type of brain cell called astrocytes may play a pivotal
role in causing some behavioral symptoms of autism spectrum disorders, according to a preclinical study by Weill Cornell Medicine investigators.


==========================================================================
For the study, published April 1 in Molecular Psychiatry, senior
author Dr.

Dilek Colak, assistant professor of neuroscience at the Feil Family
Brain and Mind Research Institute at Weill Cornell Medicine, and her
colleagues grew astrocytes from the stem cells derived from patients
with autism and transplanted them into healthy newborn mice. They found
that after the transplant, the mice developed repetitive behaviors,
a hallmark symptom of autism spectrum disorders (ASD), but they 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 characteristic of the disease.

"Our study suggests that astrocyte abnormalities might contribute to the
onset and progression of autism spectrum disorders," said Dr. Colak, who
is also assistant professor of neuroscience in pediatrics and a member of
the Drukier Institute for Children's Health. "Astrocyte abnormalities may
be responsible for repetitive behavior or memory deficits, but not other symptoms like difficulties with social interactions." Most studies
of autism spectrum disorders have focused on the role of neurons,
a type of brain cell that relays information in the brain. But other
brain cells, called astrocytes, help regulate the behavior of neurons
and the connections between them. Genetic mutations linked to autism
spectrum disorders are likely to affect various types of cells in the
brain differently, Dr. Colak said. Post-mortem studies had already
revealed abnormalities in astrocytes in the brains of patients with
autism spectrum disorders.

"We didn't know if these astrocyte abnormalities contributed to the
development of the disease or if the abnormalities are the result of
disease," Dr. Colak said.

To determine if astrocytes might be involved early in the disease,
the team obtained stem cells derived from patients with autism spectrum disorders, coaxed them into developing into astrocytes in the laboratory,
and transplanted them into the brains of otherwise healthy newborn mice, creating a human-mouse chimera.

Using a microscopic technique called two-photon imaging, they observed excessive calcium signaling in the transplanted human astrocytes in the
brains of mice, explained co-lead author Dr. Ben Huang, instructor of neuroscience in psychiatry at Weill Cornell Medicine.

"It was amazing to see these human astrocytes responding to behavioral
changes in active mice," Dr. Huang said. "We believe we are the first
to record the activity of transplanted human astrocytes this way."
To determine if the increased calcium signaling was causing the mice's behavioral symptoms, the team infected astrocytes grown from ASD
patient stem cells in the laboratory with a virus carrying a fragment
of RNA designed to reduce calcium signaling to normal levels. When they transplanted these astrocytes into the mice, the animals did not develop
memory problems.

"Future therapies for autism might exploit this finding by using genetic
tools to limit extreme calcium fluctuations inside astrocytes," said
co-lead author Megan Allen, a postdoctoral associate in neuroscience
in the Feil Family Brain and Mind Research Institute at Weill Cornell
Medicine.

The discoveries may also have important implications for understanding
and treating other neuropsychiatric diseases like schizophrenia that
also involve memory deficits, said Dr. Colak.

"It is important to determine the roles of specific types of brain
cells, including astrocytes, in neurodevelopmental and neuropsychiatric diseases," she said.


========================================================================== Story Source: Materials provided by Weill_Cornell_Medicine. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. 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, Dilek Colak. Astrocytes derived from
ASD individuals alter behavior and destabilize neuronal activity
through aberrant Ca2+ signaling. Molecular Psychiatry, 2022; DOI:
10.1038/s41380- 022-01486-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220421141557.htm

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