Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To trigger a dystonic phenotype in a non-dystonic rat DYT1 model by inducing a peripheral nerve injury and to describe a new clinical scoring system for limb dystonia in this model.
Background: DYT1 dystonia is characterized by involuntary muscle contractions leading to abnormal repetitive movements and postures caused by a GAG deletion of the Tor1A gene, that has a penetrance of only 30-40%. None of the existing non-neurodegenerative rodent models of DYT1 dystonia show the typical limb-onset dystonic phenotype seen in human. Based on the hypothesis that a “second hit” such as limb overuse or peripheral injury could elicit the dystonic phenotype in genetically predisposed subjects, we induced clinically apparent dystonia in a transgenic DYT1 rat model, that harbors the full human mutant Tor1A gene and does not show dystonia per se, by a sciatic nerve injury.
Methods: Development of dystonia after sciatic nerve crush of the right hindlimb was assessed by blinded clinical scoring of both hindlimbs using a newly developed 0-5 point scoring system during tail suspension: 0: no abnormal dystonic movement; 1: hindlimb retraction and clenching of the foot/leg with episodes lasting < 3 seconds or ≤ 2 repeats of hindlimb retraction and clenching of the foot/leg; 2: hindlimb retraction and clenching of the foot/leg with episodes lasting ≥ 3 seconds or ≥ 3 repeats of hindlimb retraction and clenching of the foot/leg; 3: hindlimb retraction and clenching of the foot/leg occurring for a total of 10 seconds to < 50% of the recorded time; 4: hindlimb retraction and clenching of the foot/leg lasting a total of 50% of the recorded time; 5: hindlimb retraction and clenching of the foot/leg for a total of > 50% of the recorded time. Dystonia duration and number of dystonic retractions of both hindlimbs were added for scoring.
Results: During the first two weeks after nerve injury an increase of the dystonia score in wt and DYT1 rats was observed with a maximum score of ∼5.0 on week 2, followed by a slow decrease of dystonic movements in both genotypes. Eight weeks after nerve injury, the dystonia score decreased in wt rats down to a minimum of ∼0.4 on week 10 while the dystonia score of DYT1 transgenic rats stayed at a higher level of about ∼2.3 at the same time point.
Conclusions: This newly established clinical dystonia scoring system has the capability to reveal clinically apparent dystonia triggered by peripheral nerve injury in DYT1 transgenic rats.
To cite this abstract in AMA style:S. Knorr, K. Grundmann-Hauser, J. Volkmann, C.W. Ip. Dystonia after peripheral nerve injury in DYT1 transgenic rats [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/dystonia-after-peripheral-nerve-injury-in-dyt1-transgenic-rats/. Accessed March 2, 2024.
« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/dystonia-after-peripheral-nerve-injury-in-dyt1-transgenic-rats/