Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice.

Autor:	Yokoi F; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Dang MT; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Zhang L; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA.; Department of Biomedical Sciences, Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL, USA., Dexter KM; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Efimenko I; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Krishnaswamy S; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Villanueva M; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Misztal CI; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Gerard M; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Lynch P; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA., Li Y; Norman Fixel Institute of Neurological Diseases, McKnight Brain Institute, and Department of Neurology, College of Medicine, University of Florida, Gainesville, FL 32610-0236, USA.
Jazyk:	angličtina
Zdroj:	IBRO neuroscience reports [IBRO Neurosci Rep] 2021 Jun 12; Vol. 11, pp. 1-7. Date of Electronic Publication: 2021 Jun 12 (Print Publication: 2021).
DOI:	10.1016/j.ibneur.2021.05.003
Abstrakt:	DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A . Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia. Competing Interests: The authors declare no competing financial interests. (© 2021 The Authors.)
Databáze:	MEDLINE
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