Synaptic Dysfunction in Dystonia: Update From Experimental Models

Abstract

Dystonia, the third most common movement disorder, refers to a heterogeneous group of neurological diseases characterized by involuntary, sustained or intermittent muscle contractions re- sulting 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 gan- glia and cerebellum, including the abnormal neurotransmitters signalling, receptor trafficking and syn- aptic 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 net- work and synaptic dysfunction represent key elements in the pathophysiology of dystonia.

The pathogenesis of blepharospasm

“…As the basis of learning and memory, synaptic plasticity is one of the most important characteristics of the central nervous system. A series of previous studies have suggested that abnormal synaptic plasticity is an important factor in the pathophysiological mechanism of dystonia ( 61 – 63 ). Importantly, Martella et al ( 61 ) found that synaptic plasticity was abnormal in the striatum of a DYT1 dystonia mouse model constructed by transgenic technology.…”