FDA-approved antibiotic improves motor function in a rat hemi-parkinsonian model: Potential to extend timeline in early-stage Parkinson's disease




Salvatore, Michael
Kasanga, Ella
McElroy, Christopher
Shifflet, Marla


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Purpose: The motor deficits of Parkinson's disease (PD): bradykinesia, resting tremors, postural instability and/or rigidity are predominantly unilateral early at diagnosis, progressing bilaterally into moderate stages of the disease. In rats, unilateral impairment can be generated using the neurotoxin 6-hydroxydopamine (6-OHDA). Progression of these deficits can be evaluated to provide insight into gradual bilateral impairment and resulting neuropathological changes. This study employed two locomotor function assays: the forepaw adjusting steps (FAS), which is an 'imposed-movement' test and the open-field locomotor (OFL) test, which relies on "at-will' movement, to longitudinally evaluate bradykinesia and impact of an FDA-approved antibiotic, initiated after lesion induction, as a potential repurposed drug in a 6-OHDA model. Method: 3-month old male Sprague-Dawley rats were evaluated at four time-points after lesion induction (days 7, 14, 21 and 28). Results: The OFL tests did not reveal any significant change in activity although there was a trend towards a decrease in ambulatory counts in the lesioned group over the 4-week period. However, FAS revealed a sustained deficit in right forepaw use (~50 %) while a compensatory increase in the use of the unaffected (left) forepaw was observed. The antibiotic further increased left forepaw use although no significant improvement was seen with the OFL test. Conclusion: Lesioning of the nigrostriatal pathway led to a transient compensatory increase in left forepaw use, an effect which was sustained by antibiotic administration suggesting a benefit that may curtail the onset of bilateral impairment.