A new synapse disease discovered at the base of Autism and intellectual disabilities.
On the left: Confocal microscopy image of a cultured neuron expressing the PTCHD1 protein fused to GFP (photo above) and indicating a localization in the dendritic extensions and the synaptic (zoom) endings, the dendritic spines.
Right: Images in electron microscopy with transmission of synaptic junctions from the mouse control brain hippocampus and Ptchd1- / y (KO model), revealing in particular structural abnormalities in the mouse KO: Decrease in thickness of the postsynatic density (dark zone) and the synaptic cleft.
Mol Psychiatry May 2018
April 18, 2017
An international collaborative study coordinated by the Inserm unit 930 "Imaging and Brain" (Dr. Frédéric Laumonnier, Tours), PHENOMIN and the IGBMC (Dr. Yann Hérault, Illkirch) brings new and original data on the characterization of the physiopathological role of the synaptic receptor PTCHD1. Published on April 18 in the journal Molecular Psychiatry, this work reveals that the loss of function of this gene involved in intellectual disability and autism, leads to synaptic dysfunction.
Synapses are zones of contact between neurons, ensuring the connection and propagation of the information between them, and causing their excitation or inhibition. During the development of the brain, the formation of synapses is essential for brain functions such as memory and learning.
Genetic mutations involved in autism and intellectual disability (ID) seem to cause defects in the structure and function of these synapses.
In the Research Unit "Imaging and Brain" at François-Rabelais University in Tours, Frédéric Laumonnier and his colleagues are interested in the synaptic receptor PTCHD1 (Patched Domain containing 1), for which genetic mutations are associated with an ID and / or autism in boys. After creating a pathological mouse model deficient for this gene, scientists from PHENOMIN and the IGBMC showed major memory defects, as well as significant symptoms of hyperactivity on this model. Parallel studies by the team of Frédéric Laumonnier revealed changes in the synapses. The latter discovered significant alterations in synaptic structure and activity in excitatory neuronal networks of the hippocampus, a region of the brain that plays a major role in cognitive processes.
This work defines a new synapse disease occurring during development, in technical terms a neuro-developmental synaptopathy, caused by the deficiency of the PTCHD1 gene associated with ID and autism. Understanding the pathophysiological mechanisms underlying these neurodevelopmental disorders is essential to improve therapeutic strategies.