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.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dystonia-after-peripheral-nerve-injury-in-dyt1-transgenic-rats/