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      Deficit of Striatal Parvalbumin-Reactive GABAergic Interneurons and Decreased Basal Ganglia Output in a Genetic Rodent Model of Idiopathic Paroxysmal Dystonia

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          Abstract

          The underlying mechanisms of various types of hereditary dystonia, a common movement disorder, are still unknown. Recent findings in a genetic model of a type of paroxysmal dystonia, the dt sz mutant hamster, pointed to striatal dysfunctions. In the present study, immunhistochemical experiments demonstrated a marked decrease in the number and density of parvalbumin-immunoreactive GABAergic interneurons in all striatal subregions of mutant hamsters. To examine the functional relevance of the reduction of these inhibitory interneurons, the effects of the GABA A receptor agonist muscimol on severity of dystonia were examined after microinjections into the striatum and after systemic administrations. Muscimol improved the dystonic syndrome after striatal injections to a similar extent as after systemic treatment, supporting the importance of the deficiency of striatal GABAergic interneurons for the occurrence of the motor disturbances. The disinhibition of striatal GABAergic projection neurons, as suggested by recent extracellular single-unit recordings in dt sz hamsters, should lead to an abnormal neuronal activity in the basal ganglia output nuclei. Indeed, a significantly decreased basal discharge rate of entopeduncular neurons was found in dt sz hamsters. We conclude that a deficit of striatal GABAergic interneurons leads by disinhibition of striatal GABAergic projection neurons to a reduced activity in the entopeduncular nucleus, i.e., to a decreased basal ganglia output. This finding is in line with the current hypothesis about the pathophysiology of hyperkinesias. The results indicate that striatal interneurons deserve attention in basic and clinical research of those movement disorders.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 September 2000
          : 20
          : 18
          : 7052-7058
          Affiliations
          [ 1 ]Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, 30559 Hannover, Germany
          Article
          PMC6772842 PMC6772842 6772842 4508
          10.1523/JNEUROSCI.20-18-07052.2000
          6772842
          10995851
          17919c45-451c-441d-a4af-02f411520e60
          Copyright © 2000 Society for Neuroscience
          History
          : 2 May 2000
          : 27 June 2000
          : 28 June 2000
          Categories
          ARTICLE
          Behavioral/Systems
          Custom metadata
          5.00

          parvalbumin,dyskinesia,immunohistochemistry,GABA,basal ganglia,animal models,dystonia,striatum,electrophysiology,muscimol,movement disorders,entopeduncular nucleus,interneurons

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