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Of Mice and Men

Scientists from the NeuroCure Excellence Cluster Characterize New Autism Gene

№ 110/2012 from May 03, 2012

Malfunctioning single proteins can cause disruptions in neuronal junctions leading to autistic forms of behavior. A current study, published in the scientific journal Nature, comes to this conclusion after examining genetically altered mice. The study, in which scientists from Charité – Universitätsmedizin Berlin, the joint medical school of Freie Universität Berlin and Humboldt-Universität zu Berlin, and the NeuroCure Cluster of Excellence contributed, thus supports the hypothesis that disruptions in neuronal junctions, i.e. synapses, could be the cause of the development of neuropsychiatric illnesses like autism. The international research team, that included scientists from Ulm University and the Institut Pasteur in Paris, ascribes a key role to the excitatory synapses. This finding could become an important stepping stone for future autism therapies. NeuroCure is one of four excellence clusters in which Freie Universität is involved.

Nerve cells communicate with each other via signal transmission to synaptic junctions. These junctions are stabilized through structural proteins, including the so-called ProSAP1/Shank2 protein. In order to understand the role that this protein has on synapses and ultimately in the development of autism, the researchers genetically modified mice and disabled the relevant protein. The choice of this protein was not arbitrary: In preparation for the current study, a number of the scientists involved found evidence that the mutation of this protein can lead to autism in humans. Various neuronal developmental disorders manifested through distinctive social and communicative behavioral features, as well as stereotyped behaviors are combined under the term of “autism.”

The absence of this structural protein in the mouse model also had visible implications: Animals with the mutated gene are hyperactive and demonstrate compulsive repetitions of particular features, like grooming, for example. In behavioral experiments, peculiarities in social and communicative interaction also become distinct.

In the brains of the mice, researchers found noticeable mutations of synaptic junctions, specifically in excitatory synapses. When glutamate transmitters bind to glutamate receptors located at these junctions, the nerve cells become excitatory. If the mouse is lacking this structural protein, the transmitters increasingly find a related structural protein on the excitatory synapses, the ProSAP2/Shank3. This protein has also been implicated in the development of autism. At the same time, the composition of glutamate receptors mutates.

But what happens when this related structural protein in the mice is switched off? This is also examined in the study presented. The conclusion is that, in this case as well, mutations of the excitatory synapses occur. Obviously, both structural molecules alternate in fulfilling regular functions.

“The study illustrates the significant role glutamatergic systems play in autism and thus contributes to understanding better synaptic changes in autism,” reports Stephanie Wegener, one of the participating scientists at Charité Berlin. The study is therefore an important part of the essential scientific foundation needed to develop possible therapies for autism.

NeuroCure is a Cluster of Excellence at Charité – Universitätsmedizin Berlin funded by the German federal and state government within the framework of the Excellence Initiative. The focus of the interdisciplinary research network is to translate basic neuroscientific research findings into clinical application. Understanding the mechanisms of disease contributes to developing effective therapies for neurological illnesses like strokes, multiple sclerosis and epilepsy. In addition to Charité, Humboldt-Universität zu Berlin, Freie Universität Berlin, Max Delbrück Center for Molecular Medicine (MDC), Leibniz Institute for Molecular Pharmacology (FMP), and Deutsche Rheuma-Forschungszentrum Berlin (DRFZ) are all NeuroCure partners.

Further Information

  • Prof.Dr. Dietmar Schmitz, Spokesperson, NeuroCure Cluster of Excellence, Charité – Universitätsmedizin Berlin, Tel.: +49 (0)30 / 450539054, Email: 
  • Prof. Dr. Tobias M. Böckers, Ulm University, Tel.: 49 (0)731 / 50023220, Email: