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University of Basel

05 August 2020

Autism: How a gene alteration modifies social behavior

Outlines of a head and the brain drawn with chalk on asphalt
A certain gene mutation in autism alters the effect of the "social hormone" oxytocin in the brain. (Symbolic image: shutterstock)

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.

microscopic image of red and blue fluorescent cells
Oxytocin producing neurons (red) in the mouse brain. (Photo: University of Basel, Biozentrum)

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.

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