Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice
العنوان: | Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice |
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المؤلفون: | Mai Tu Dang, Carly I. Misztal, Iakov Efimenko, Matthew Villanueva, Lin Zhang, Kelly M. Dexter, Shiv Krishnaswamy, Malinda Gerard, Fumiaki Yokoi, Patrick Lynch, Yuqing Li |
المصدر: | IBRO Neuroscience Reports, Vol 11, Iss, Pp 1-7 (2021) IBRO Neuroscience Reports |
بيانات النشر: | Elsevier, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | medicine.medical_specialty, LTD, long-term depression, ChAT, choline acetyltransferase, Trihexyphenidyl, Dyt1 KI mice, Dyt1 ΔGAG heterozygous knock-in mice, Motor learning, PB, phosphate buffer, PBS, phosphate-buffered saline, ChI, cholinergic interneuron, Neurosciences. Biological psychiatry. Neuropsychiatry, TOR1A, Article, n.s., not significant, PET, positron emission tomography, TrkA, tropomyosin receptor kinase A, THP, trihexyphenidyl, AChE, acetylcholinesterase, Gene knockin, Internal medicine, GAPDH, Glyceraldehyde-3-phosphate dehydrogenase, Medicine, Rotarod, Dystonia, KO, knockout, DAB, 3,3′-diaminobenzidine, ACh, acetylcholine, business.industry, General Neuroscience, Antagonist, DF, degrees of freedom, Muscarinic acetylcholine receptor M1, medicine.disease, WT, wild-type, CI, confidence interval, Endocrinology, TorsinA, Excitatory postsynaptic potential, Cholinergic, BSA, bovine serum albumin, VAChT, vesicular acetylcholine transporter, business, ChT, choline transporter, Cholinergic interneuron, medicine.drug, RC321-571 |
الوصف: | 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. |
اللغة: | English |
تدمد: | 2667-2421 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf995925b903998cc00bb08dddbee16d http://www.sciencedirect.com/science/article/pii/S2667242121000233 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....cf995925b903998cc00bb08dddbee16d |
قاعدة البيانات: | OpenAIRE |
تدمد: | 26672421 |
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