November 11, 2021

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by: admin

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Tags: Adult, Autismlinked, gene, mice, mutations, Reversing, Social, Spectrum, Top

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Categories: autism

Reversing mutations in high autism-linked gene makes grownup mice extra social | Spectrum

Increased interest: SCN2A-deficient mice are more likely to socialize like control mice after a mutation in the gene has been corrected.

Georgejason / iStock

Treatments that counteract the effects of a mutation in an autism-related gene in mice increase the sociability of animals in adulthood, according to a new unpublished study.

The researchers presented the results virtually at the Society for Neuroscience’s annual meeting in 2021.

The results are based on mice lacking SCN2A, a gene that codes for an ion channel protein that carries electrical signals through the brain. Mutations in the gene are strongly linked to autism and often cause epilepsy.

Mice lacking both copies of SCN2A usually do not survive long after birth, while those lacking only one copy show little behavioral differences from control mice, according to previous work.

To create a useful model for the new study, the researchers used a “gene trap,” a snippet of DNA that alters gene expression. Mice constructed with the gene trap express approximately 25 percent of typical SCN2A levels. The trap also enabled the researchers to later restore typical expression levels of the gene in adult mice and to change their behavior.

Social changes:

In contrast to control mice with two working copies of the gene, the SCN2A model mice preferred to spend time in an empty chamber rather than with another mouse, which suggests less social interest.

However, when the researchers injected a transgene into the animals’ tails to block the gene trap, the SCN2A mice and the control mice socialized in a similar manner.

In order to isolate the responsible part of the brain, the researchers next injected the transgene only into the striatum, but this had no effect. The animals’ social behavior improved again, however, when the team introduced the transgene into areas connecting the striatum to the hippocampus, thalamus, and the prefrontal cortex.

The animals’ social behavior also increased when treated with the anti-anxiety drug clonazepam or another compound that inhibits the excitatory neurons that connect the medial prefrontal cortex and striatum.

The results show that “treatments can work in adults,” says Muriel Eaton, a PhD student in Yang Yang’s laboratory at Purdue University in West Lafayette, Indiana, who presented the work.

Cellular Shifts:

In a second study, Eaton and her colleagues show that the mice also have learning and memory disorders and that neurons in their hippocampus have unusually few branches to other neurons. Further analysis suggested that this problem appears to be due to differences in the animals’ microglia – non-neural brain cells that help protect neurons from damage and form neural connections.

The microglia results explain the electrophysiological basis of social behavior change, says Eaton.

According to another study presented at the conference, a drug also altered electrical activity in brain slices from mice that were missing a copy of SCN2A from SCN2A.

Eaton says she and her colleagues are working on adapting virus-based gene therapy to get a functional copy of SCN2A into the mice – a strategy being developed for other conditions like fragile X and Rett syndrome.

“You can’t go straight to clinical trials with it,” says Eaton, “but it’s another step.”

Read more reports from the Society for Neuroscience’s 2021 Annual Virtual Meeting.

Quote this article: https://doi.org/10.53053/GFZD8927

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