Blockage of the Proposed Precipitating Stage for Parkinson's Disease by Antioxidants: A Potential Preventative Measure for PD

Abstract

Parkinson's disease (PD) is due to the degeneration of dopamine (DA) neurons and loss of nigrostriatal (NS) tyrosine hydroxylase (TH) and DA. In another study we show that fetal exposure to toxins makes the NS DA neurons vulnerable and that later challenges cause the vulnerable neurons to succumb, indicative of a sensitization stage and a precipitating stage for idiopathic PD. In this study we determine whether the precipitating stage can be blocked by treating with antioxidants, as a potential preventative measure for PD. Adult mice were treated every other day for 27 days with 25 or 50 μg/animal of curcumin (CU) or with 25 or 50 mg/kg BW of an antioxidant cocktail (AO). The goal was to know if CU or AO can block the TH depleting effects of MPTP, so at the 20th day treatment point a 7 day 30 mg/kg/day of MPTP was included. Western blot for TH, brain histology and motor activities were determined. The treatments with CU and AO block, in a dose‐dependent manner, the TH‐depleting effects and the hypokinesia of MPTP. MPTP depletes TH by about 60 and 80% in the striatum and midbrain. In the striatum and midbrain CU substantially and partially blocks the effects of MPTP and AO blocks the effects of MPTP and may enhance TH expression. Both CU and AO reduce the incidence of death and hypokinesia caused by MPTP. The results demonstrate that pre‐symptoms therapeutic interventions may be effective in blocking or delaying the on‐set of PD. Supported by NIH RO1NS041674 and NIH R21NS049623