@article{2908392fdb334207a5d501766e4e2fb7,
title = "Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice",
abstract = "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.",
keywords = "Cholinergic interneuron, Dystonia, Motor learning, Rotarod, TOR1A, TorsinA",
author = "Fumiaki Yokoi and Dang, {Mai Tu} and Lin Zhang and Dexter, {Kelly M.} and Iakov Efimenko and Shiv Krishnaswamy and Matthew Villanueva and Misztal, {Carly I.} and Malinda Gerard and Patrick Lynch and Yuqing Li",
note = "Funding Information: We thank Andrea McCullough and their staff for animal care, Miki Jinno, Jessica Artille, Jareisha Vickers, Aysha Awal, Alyka Glor Fernandez, and other undergraduate students for their technical assistance. This work was supported by Tyler{\textquoteright}s Hope for a Dystonia Cure, Inc., “Mini-Moonshot” Fixel-MBI Pilot Grant Mechanism for Dystonia and Related Disorders, National Institutes of Health ( NS54246 , NS72782 , NS75012 , NS82244 , NS111498 , and NS118397 ), startup funds from the Department of Neurology (UAB and UF), Dystonia Medical Research Foundation , and Bachmann-Strauss Dystonia and Parkinson Foundation, Inc. , and Department of Defense ( W81XWH1810099 ). FY was partially supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer-Reviewed Medical Research Program Discovery Award. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Funding Information: We thank Andrea McCullough and their staff for animal care, Miki Jinno, Jessica Artille, Jareisha Vickers, Aysha Awal, Alyka Glor Fernandez, and other undergraduate students for their technical assistance. This work was supported by Tyler's Hope for a Dystonia Cure, Inc. ?Mini-Moonshot? Fixel-MBI Pilot Grant Mechanism for Dystonia and Related Disorders, National Institutes of Health (NS54246, NS72782, NS75012, NS82244, NS111498, and NS118397), startup funds from the Department of Neurology (UAB and UF), Dystonia Medical Research Foundation, and Bachmann-Strauss Dystonia and Parkinson Foundation, Inc., and Department of Defense (W81XWH1810099). FY was partially supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Peer-Reviewed Medical Research Program Discovery Award. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = dec,
doi = "10.1016/j.ibneur.2021.05.003",
language = "English",
volume = "11",
pages = "1--7",
journal = "IBRO Neuroscience Reports",
issn = "2667-2421",
}