Synaptic Dysfunction in Dystonia: Update From Experimental Models

Abstract

Abstract: Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent muscle contractions resulting in repetitive twisting movements and abnormal postures. In the last few years, several studies on animal models helped expand our knowledge of the molecular mechanisms underlying dystonia. These findings have reinforced the notion that the synaptic alterations found mainly in the basal ganglia and cerebellum, including the abnormal neurotransmitters signalling, receptor trafficking and synaptic plasticity, are a common hallmark of different forms of dystonia. In this review, we focus on the major contribution provided by rodent models of DYT-TOR1A, DYT-THAP1, DYT-GNAL, DYT/ PARK-GCH1, DYT/PARK-TH and DYT-SGCE dystonia, which reveal that an abnormal motor network and synaptic dysfunction represent key elements in the pathophysiology of dystonia.