Some Autism-Like Behaviors Disappear in Adult Mice After Switching on the Shank3 Gene

Some Autism-Like Behaviors Disappear in Adult Mice After Switching on the Shank3 Gene

Posted: May 13, 2016

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By flipping a genetic switch, researchers were able to eliminate some autism-like behaviors in adult mice, suggesting that the adult brain might still have some degree of plasticity and that some autism-related behaviors may be reversible, according to a new study published February 17, 2016 in Nature.

A key question in autism research is whether abnormalities that occur during brain development in people who go on to develop autism are reversible in adulthood. One of the genes associated with autism is called Shank3, which plays a role in the development of synapses, the communication junctions between brain cells. Mutations in this gene are found in about 1 percent of people with autism. Mice lacking a functioning Shank3 gene develop autism-like signs including repetitive grooming, anxiety, and problems with social interaction.

In the new study, a team led by Guoping Feng, Ph.D., of Massachusetts Institute of Technology, and including Zhanyan Fu, Ph.D., of the Broad Institute of MIT and Harvard, a 2012 NARSAD Young Investigator grantee, created mice with a turned-off Shank3 gene. In their mouse model, the gene could later be switched back on.

As expected, the mice with the turned-off Shank3 gene differed from typical juvenile mice; they showed high anxiety and repetitive behavior, reduced interest in exploring their surroundings, and problems in coordinating their movements.

When the mice reached two to four months of age – such mice typically have a lifespan of 2-3 years -- the researchers gave some of the animals a drug to reactivate the Shank3 gene. After doing so, the treated mice became more social and stopped repetitive grooming. Mice that had initially developed skin lesions due to excessive grooming began to heal and regrow their lost fur. However, their movement problems and anxiety persisted.

Looking at the brain, the researchers found that turning on the Shank3 gene led to an improvement of neural function, protein composition, and density of small features on dendrites called dendritic spines that receive information from other cells. These changes occurred in the striatum, part of the brain where the Shank3 gene is especially active.

Together, these findings reveal the effects of activating Shank3 in adulthood after the brain’s developmental stage has passed, highlighting the surprising extent of continued neural plasticity in the adult brain, the researchers said.

Takeaway: Autism-like behaviors in adult mice are reversible by switching on and off a gene called Shank3, one of the genes associated with autism.