Estrogen modulation of MPP+- induced Dopamine secretion in the Corpus Striatum and Nucleus accumbens of the Rat Brain, /

Abstract

Parkinson's disease, first described in 1817, is a progressive disorder affecting men and women of middle age and older. The disease results in a disruption of normal motor function. Classic features include muscle rigidity, resting tremor, and the inability to initiate normal muscle movement. These symptoms are the result of the destruction of dopamine producing neurons in an area of the brain known as the Substantia Nigra and the subsequent depletion of dopamine in the striatum. The cause of the disorder is still unknown. Possible contributing factors proposed include environmentally acquired toxins, and/or endogenous toxic

metabolic byproducts. There is also the possibility of a genetic component predisposing certain individuals to the disorder. This study was designed to investigate the modulatory and possible neuroprotective effects of the steroid hormone estrogen upon dopamine release and clearance from neurons of the nigrostriatal system. An in vivo animal model, along with the technique of in vivo electrochemistry was used to demonstrate, in real time, the characteristics of dopamine release and clearance. This is accomplished through the use of a stereotaxic instrument which allows for the placement of an electrode and micropipette assembly into specific brain regions. A neurotoxin, MPP+, which simulates the biochemical events seen in Parkinson's disease was used to stimulate the release of dopamine from the nigrostriatal neurons. Female ovarectomized rats were divided into two treatment groups, MPP+ alone, and MPP+ with estrogen. These treatments were applied to the rat forebrain and measurements of the ensuing dopamine release were monitored using the lVEC-l 0 system and software capable of measuring neurochemical substances such as dopamine. Results of this study demonstrate a modulatory and/or neuroprotective effect of estrogen upon neurons of the nigrostriatal pathway by decreasing the effectiveness ofMPP+ to elicit the release of dopamine from these neurons. The results of this study also reveal differences, in some release and clearance parameters, between the corpus striatum and nucleus accumbens.