Striatal dopaminergic dysregulation and dystonia-like movements induced by sensorimotor stress in a pharmacological mouse model of rapid-onset dystonia-parkinsonism.

Striatal dopaminergic dysregulation and dystonia-like movements induced by sensorimotor stress in a pharmacological mouse model of rapid-onset dystonia-parkinsonism. Exp Neurol. 2019 Nov 08;:113109 Authors: Rauschenberger L, Knorr S, Al-Zuraiqi Y, Tovote P, Volkmann J, Ip CW Abstract Rapid-onset dystonia-parkinsonism (RDP) is a rare form of hereditary dystonia caused by loss-of-function mutations of the Na+/K+-ATPase α3 isoform (ATP1α3). An acute onset of generalized dystonia and parkinsonism after exposure to stress and an incomplete disease penetrance is described in RDP, thereby suggesting a gene-environmental interaction in individuals with a genetic predisposition for dystonia development. Dystonia is considered a central motor network disease and in line with this concept, alterations in cerebellar neuronal firing have been described in RDP mouse models, but the pathogenic role of the basal ganglia remains unclear. We have mimicked RDP pharmacologically by simultaneous perfusion of the selective ATP1α3-blocker ouabain into the striatum and cerebellum of mice, followed by repeated exposure to mild motor stress. Ouabain-perfused RDP mice developed dystonia-like movements, which were exacerbated by exposure to sensorimotor stress. Compared to control mice, ouabain perfusion of the striatum led to dendritic spine loss of medium spiny neurons in addition to loss of cholinergic and GABAergic interneurons in the striatum. High-pres...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research