Longitudinal assessment of skilled forelimb motor impairments in DJ-1 knockout rats

Abstract

BackgroundDJ-1 knockout (DJ-1 KO) rats exhibit a moderate parkinsonian phenotype, with gross motor deficits and ca. 50% loss of midbrain dopaminergic neurons appearing around 6–8 months of age. Fine motor impairments are often observed in Parkinson’s disease (PD), but skilled motor function in recently developed transgenic rat models of PD is not well characterized. ObjectivesTo assess the longitudinal performance of DJ-1 KO rats on a skilled forelimb reaching task. MethodsDJ-1 KO and wild-type (WT) rats were trained from 2 to 10 months of age on an isometric pullbar task designed to test forelimb strength and coordination. After 36 consecutive weeks of training (ca. 10 months old), task difficulty was then increased to challenge the motor capabilities of the DJ-1 KO rats. Throughout the study, subjects also received weekly assessments of gross locomotor activity in an open field. ResultsPull-task performance of the DJ-1 KO rats was impaired compared to WT, with deficits reaching significance around 7–9 months of age. When challenged, DJ-1 KO rats were able to exert increased force on the pullbar but continued to exhibit deficits compared to WT rats. Throughout the study, no differences in distance traveled or rearing frequency were observed in the open field, but DJ-1 KO rats were found to spend significantly more time in the center of the open field than WT rats. ConclusionsUsing a sensitive, automated assay of forelimb strength and coordination, we find that skilled forelimb motor performance is impaired in DJ-1 KO rats.