{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yokoi F"],"funding":["Dystonia Medical Research Foundation","UIUC","UAB","NINDS NIH HHS","Bachmann-Strauss Dystonia and Parkinson Foundation, Inc.","National Institutes of Health"],"pagination":["202-10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4286880"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["279"],"pubmed_abstract":["DYT1 dystonia is a movement disorder caused by a trinucleotide deletion (ΔGAG) in DYT1 (TOR1A), corresponding to a glutamic acid loss in the C-terminal region of torsinA. Functional alterations in the basal ganglia circuits have been reported in both DYT1 dystonia patients and rodent models. Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits and decreased striatal dopamine receptor 2 (D2R) binding activity, suggesting a malfunction of the indirect pathway. However, the role of the direct pathway in pathogenesis of dystonia is not yet clear. Here, we report that Dyt1 KI mice exhibit significantly decreased striatal dopamine receptor 1 (D1R) binding activity and D1R protein levels, suggesting the alteration of the direct pathway. The decreased D1R may be caused by translational or post-translational processes since Dyt1 KI mice had normal levels of striatal D1R mRNA and a normal number of striatal neurons expressing D1R. Levels of striatal ionotropic glutamate receptor subunits, dopamine transporter, acetylcholine muscarinic M4 receptor and adenosine A2A receptor were not altered suggesting a specificity of affected polytopic membrane-associated proteins. Contribution of the direct pathway to motor-skill learning has been suggested in another pharmacological rat model injected with a D1R antagonist. In the present study, we developed a novel motor skill transfer test for mice and found deficits in Dyt1 KI mice. Further characterization of both the direct and the indirect pathways in Dyt1 KI mice will aid the development of novel therapeutic drugs."],"journal":["Behavioural brain research"],"pubmed_title":["Decreased dopamine receptor 1 activity and impaired motor-skill transfer in Dyt1 ΔGAG heterozygous knock-in mice."],"pmcid":["PMC4286880"],"funding_grant_id":["R01 NS082244","P30 NS057098","P50 NS037409","NS57098","NS37409","R01 NS054246","NS82244","NS37409, NS47466, NS47692, NS54246, NS57098, NS65273, NS72782, NS74423, and NS82244","R21 NS072872","P01 NS037409","NS65273","NS47466","NS74423","NS72782","R03 NS074423","NS47692","R21 NS065273","NS54246","R21 NS047692","P30 NS047466"],"pubmed_authors":["Liu J","Li Y","Gandre JR","Yuen R","Yokoi F","Dang MT","Kwon K"],"additional_accession":[]},"is_claimable":false,"name":"Decreased dopamine receptor 1 activity and impaired motor-skill transfer in Dyt1 ΔGAG heterozygous knock-in mice.","description":"DYT1 dystonia is a movement disorder caused by a trinucleotide deletion (ΔGAG) in DYT1 (TOR1A), corresponding to a glutamic acid loss in the C-terminal region of torsinA. Functional alterations in the basal ganglia circuits have been reported in both DYT1 dystonia patients and rodent models. Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits and decreased striatal dopamine receptor 2 (D2R) binding activity, suggesting a malfunction of the indirect pathway. However, the role of the direct pathway in pathogenesis of dystonia is not yet clear. Here, we report that Dyt1 KI mice exhibit significantly decreased striatal dopamine receptor 1 (D1R) binding activity and D1R protein levels, suggesting the alteration of the direct pathway. The decreased D1R may be caused by translational or post-translational processes since Dyt1 KI mice had normal levels of striatal D1R mRNA and a normal number of striatal neurons expressing D1R. Levels of striatal ionotropic glutamate receptor subunits, dopamine transporter, acetylcholine muscarinic M4 receptor and adenosine A2A receptor were not altered suggesting a specificity of affected polytopic membrane-associated proteins. Contribution of the direct pathway to motor-skill learning has been suggested in another pharmacological rat model injected with a D1R antagonist. In the present study, we developed a novel motor skill transfer test for mice and found deficits in Dyt1 KI mice. Further characterization of both the direct and the indirect pathways in Dyt1 KI mice will aid the development of novel therapeutic drugs.","dates":{"release":"2015-01-01T00:00:00Z","publication":"2015 Feb","modification":"2024-11-20T22:04:02.482Z","creation":"2019-03-27T01:42:55Z"},"accession":"S-EPMC4286880","cross_references":{"pubmed":["25451552"],"doi":["10.1016/j.bbr.2014.11.037"]}}