Quantitation of Hydrogen Peroxide Fluctuations andTheir Modulation of Dopamine Dynamics in the Rat Dorsal Striatum UsingFast-Scan Cyclic Voltammetry

摘要

The dopaminergic neurons of the nigrostriatal dopamine (DA) projection from the substantia nigra to the dorsal striatum become dysfunctional and slowly degenerate in Parkinson’s disease, a neurodegenerative disorder that afflicts more than one million Americans. There is no specific known cause for idiopathic Parkinson’s disease; however, multiple lines of evidence implicate oxidative stress as an underlying factor in both the initiation and progression of the disease. This involves the enhanced generation of reactive oxygen species, including hydrogen peroxide (H2O2), whose role in complex biological processes is not well understood. Using fast-scan cyclic voltammetry at bare carbon-fiber microelectrodes, we have simultaneously monitored and quantified H2O2 and DA fluctuations in intact striatal tissue under basal conditions and in response to the initiation of oxidative stress. Furthermore, we have assessed the effect of acute increases in local H2O2 concentration on both electrically evoked DA release and basal DA levels. Increasesin endogenous H2O2 in the dorsal striatum attenuatedelectrically evoked DA release, and also decreased basal DA levelsin this brain region. These novel results will help to disambiguatethe chemical mechanisms underlying the progression of neurodegenerativedisease states, such as Parkinson’s disease, that involve oxidativestress.