Autism: How a gene alteration modifies social behavior

August 05, 2020

A team of researchers at the Biozentrum, University of Basel, has discovered a new connection between a genetic alteration and social difficulties related to autism: A mutation in the neuroligin-3 gene reduces the effect of the hormone oxytocin. In the journal Nature, the researchers report on a treatment approach that could normalize social behavior in autism. They have already achieved promising results in an animal model.

Autism occurs in about one percent of the population and is characterized by alterations in communication, repetitive behavior and social difficulties. There are numerous genetic factors involved in the development of autism. Hundreds of different genes have been identified, including the gene encoding the synaptic adhesion molecule neuroligin-3. The mechanisms by which this large variety of genetic alterations is related to the symptoms of autism are still largely unknown and is one of the major challenges in the development of new treatments.

The research team led by Professor Peter Scheiffele at the Biozentrum of the University of Basel has now uncovered an unexpected link between neuroligin-3, a gene that contributes to the likelihood of autism, and the oxytocin signaling pathway in a mouse model. The hormone oxytocin regulates social behavior in mammals, in particular social interactions.

Mutation affects how neurons respond

Mice with mutations in certain genes which display a typical behavior linked to autism in humans are used as a model system to study autism and help scientists to learn more about the biology of this condition in humans.

In such a mouse model, Scheiffele's team has demonstrated for the first time that an autism associated mutation in the neuroligin-3 gene disrupts the oxytocin signaling pathway in the neurons of the brain's reward system in mice and, as a consequence, reduces social interactions between mice. Unexpectedly, loss of neuroligin affects the balance of protein synthesis in these neurons and thus the neuronal responses to oxytocin.

It was already speculated that signals mediated by oxytocin could possibly play a role in autism. "However, we were very surprised to discover that mutations in neuroligin-3 impair oxytocin signaling pathways. We have succeeded in putting together two puzzle pieces of the mechanisms underlying autism," says Scheiffele.

Altered oxytocin signaling is reversible

Furthermore, the research team demonstrated that alterations in the oxytocin system in mice with a neuroligin-3 mutation can be restored by treatment with a pharmacological inhibitor of protein synthesis. This treatment normalized the social behavior of the mice: Like their healthy conspecifics, they reacted differently to familiar mice or mice foreign to them. Importantly, the same inhibitor also improved behavioral symptoms in a second rodent model of autism, indicating that it could be more widely applied in the treatment of autism.

The newly discovered convergence between three important elements - a genetic factor, the changes in neuronal protein synthesis, and the regulation of social behavior by the oxytocin system -sheds some light onto how multiple factors implicated in autism may be connected. In addition, the findings may open new approaches for the treatment of certain aspects of social behavior in some cases of autism, where this is desirable.
-end-


University of Basel

Related Autism Articles from Brightsurf:

Autism-cholesterol link
Study identifies genetic link between cholesterol alterations and autism.

National Autism Indicators Report: the connection between autism and financial hardship
A.J. Drexel Autism Institute released the 2020 National Autism Indicators Report highlighting the financial challenges facing households of children with autism spectrum disorder (ASD), including higher levels of poverty, material hardship and medical expenses.

Autism risk estimated at 3 to 5% for children whose parents have a sibling with autism
Roughly 3 to 5% of children with an aunt or uncle with autism spectrum disorder (ASD) can also be expected to have ASD, compared to about 1.5% of children in the general population, according to a study funded by the National Institutes of Health.

Adulthood with autism
The independence that comes with growing up can be scary for any teenager, but for young adults with autism spectrum disorder and their caregivers, the transition from adolescence to adulthood can seem particularly daunting.

Brain protein mutation from child with autism causes autism-like behavioral change in mice
A de novo gene mutation that encodes a brain protein in a child with autism has been placed into the brains of mice.

Autism and theory of mind
Theory of mind, or the ability to represent other people's minds as distinct from one's own, can be difficult for people with autism.

Potential biomarker for autism
A study of young children with autism spectrum disorder published in JNeurosci reveals altered brain waves compared to typically developing children during a motor control task.

Autism often associated with multiple new mutations
Most autism cases are in families with no previous history of the disorder.

State laws requiring autism coverage by private insurers led to increases in autism care
A new study led by researchers at the Johns Hopkins Bloomberg School of Public Health has found that the enactment of state laws mandating coverage of autism spectrum disorder (ASD) was followed by sizable increases in insurer-covered ASD care and associated spending.

Autism's gender patterns
Having one child with autism is a well-known risk factor for having another one with the same disorder, but whether and how a sibling's gender influences this risk has remained largely unknown.

Read More: Autism News and Autism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.