Disorder of Neural Circuits in Autism Mouse Model is Reversible

People with autism suffer from a pervasive developmental disorder of the brain that becomes evident in early childhood. Peter Scheiffele and Kaspar Vogt, Professors at the Biozentrum of the University of Basel, have now identified a specific dysfunction in neuronal circuits that is caused by autism. In the respected journal Science, the scientists also report about their success in reversing these neuronal changes. These findings are an important step in drug development for the treatment for autism.

According to current estimates, about one percent of all children develop an autistic spectrum disorder. Individuals with autism may exhibit impaired social behaviour, rigid patterns of behaviour and limited speech development. Autism is a hereditary developmental disorder of the brain. A central risk factor for the development of autism are numerous mutations in over 300 genes including the gene neuroligin-3, which is involved in the formation of synapses, the contact junction between nerve cells.

Loss of neuroligin-3 interferes with neuronal signal transmission

The consequences of neuroligin-3 loss can be studied in animal models. Mice lacking the gene for neuroligin-3 develop behavioural patterns reflecting important aspects observed in autism. In collaboration with Roche, the researchers from the Biozentrum at the University of Basel have now identified a defect in synaptic signal transmission in these mice that interferes with the function and plasticity of the neuronal circuits. Stephane Baudouin, the first author of this study, could trace the negative effect back to the increased production of a specific neuronal glutamate receptor, which modulates the signal transmission between neurons. An excess of these receptors inhibits the adaptation of the synaptic signal transmission during the learning process, thus disrupting the development and function of the brain in the long term.

Neurons of the mouse brain modeled for autism are shown.
Synaptic connections in the brain of a mouse modeled for autism. Image adapted from photo credited to Stephane Baudoin.

Of major importance is the finding that the impaired development of the neuronal circuit in the brain is reversible. When the scientists reactivated the production of neuroligin-3 in the mice, the nerve cells scaled down the production of the glutamate receptors to a normal level and the structural defects in the brain typical for autism disappeared. Hence, these glutamate receptors could be a suitable pharmacological target in order to stop the developmental disorder autism or even reverse it.

Vision for the future: Medication for autism

Autism currently cannot be cured. At present, only the symptoms of the disorder can be alleviated through behavioural therapy and other treatment. A new approach to its treatment, however, has been uncovered through the results of this study. In the European Union supported project EU-AIMS, the research groups from the Biozentrum are working in collaboration with Roche and other partners in industry on applying glutamate receptor antagonists for the treatment of autism.

Notes about this Autism research

Contacts: Katrin Bühler – University of Basel
Prof. Dr. Peter Scheiffele – University of Basel Lab
Source: University of Basel press release
Image Source: Mouse model for Autism image adapted from University of Basel image credited to Stephane Baudouin.
Original Research: Abstract for “Shared Synaptic Pathophysiology in Syndromic and Non-syndromic Rodent Models of Autism” by Stéphane J. Baudouin, Julien Gaudias, Stefan Gerharz, Laetitia Hatstatt, Kuikui Zhou, Pradeep Punnakkal, Kenji F. Tanaka, Will Spooren, Rene Hen, Chris I. De Zeeuw, Kaspar Vogt and Peter Scheiffele online 13 September 2012 doi:10.1126/science.1224159

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