Fragile X syndrome is the most common inherited cause of intellectual disability. It is more common in boys (1 in 4000) than girls (1 in 6000). In addition to the intellectual disability patients often exhibit behavioral abnormalities including hyperactivity and behavior similar to autism. Patients with this syndrome are usually physically healthy and have a normal life expectancy. Patients with fragile X syndrome have an abnormality on the X chromosome. This creates a weak connection between the nerve cells and signals from the neurons are not passed properly. The underlying cause is that a particular protein is missing in the brain, namely the Fragile X Mental Retardation Protein (FMRP). In the first part, the researcher used two behavioral tests to measure aberrant social behavior in a mouse model of fragile X syndrome. In the second part, the researcher tested a treatment in the mouse model that specifically acts on the distorted signaling in the brain. After treatment with a so-called mGluR5 antagonist an improvement of the abnormal social behavior was observed. In addition to the improvements in behavior, a significant difference in a signal protein which is involved in the mGluR5 signaling, was also found, this may be further developed into a new biochemical marker in fragile X research.

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Keywords fragile X syndrome, intellectual disability, autism, social behavior, mGluR5 signalling
Promotor R. Willemsen (Rob)
Publisher Publication of this thesis was financially supported by: Erasmus University Rotterdam, Department of Clinical Genetics, Erasmus MC J.E. Jurriaanse Stichting Benedictus, the Netherlands Novartis Pharma B.V.
ISBN 978-94-6182-448-6
Persistent URL hdl.handle.net/1765/51547
de Esch, C.E.F. (2014, June 25). Therapeutic Targets and Translational Endpoints in Fragile X Syndrome. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/51547