DJ-1 function and oxidative stress (Inter-lab project)

National Institute On Aging

Investigators

Linked publications, trials & patents

Abstract

We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. In the current period, we have explored the effects of DJ-1 deficiency in the brains of mice and rats. We find that loss of DJ-1 alters cellular signaling pathways that result, at a cellular level, in the accumulation of changes in metabolic enyzmes. we have focused on crossing DJ-1 and NQO1 animals, both of which have been shown previously to have protective effects against oxidative damage in parkinsonian-related in vitro or in vivo models. To determine whether these targets have a synergistic effect, homozygous DJ-1 (n = 15), NQO1 (n = 16), and DJ-1/NQO1 (n = 18) knockout mice were phenotypically characterized against wildtype (WT; n = 18) mice across a variety of behavioral tasks. Male and female adult mice (12 24 months) were tested for basal differences in the following motor- and cognitive-related tasks: rotarod (motor learning), exploratory motor behavior (open field), grip strength (forelimb strength), cage top wire hang (motor deficit), DigiGait (gait analysis), and Y-maze spontaneous alternation (working memory and spontaneous locomotion). These tasks were chosen to encompass the wide range of motor deficits and cognitive decline seen in PD patients. All behavioral testing has recently been completed and show some mild changes in anxiety-related measures . Very excitingly, assays of fine motor skill appear to show a synergistic effect of the double knockouts, suggesting a PD-like phenotype