Glutamateric Compensatory Mechanisms Following Injury to the Basal Ganglia

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Jakowec, Michael W., Ph.D.
University of Southern California, Los Angeles, CA

Abstract

Dr. Michael Jakowec, whose MPTP studies were funded be the PDF last year at the Parkinson’s Institute, will continue this work at USC in Los Angeles.  It is known that mice are acutely (short-term) but not chronically affected by MPTP; what is not known are the compensatory mechanisms that prevent the long-term effects seen in other laboratory and clinical subjects.  He thinks that such attributes have a role in lthe preclinical or presymptomatic stage of human PD, “holding off” so to speak the results of dopaminergic losses in the striatum,  It is his goal to define the psooible contributions to these preventive mechanisms of non-DA systems such as that of glutamate, possibly leading to methods of neuroprotection.

Progress Report (as of 8/2002)

(University of Southern California) discovered increased activation of the glutamatergic (another neurotransmitter) system in neurons that survived injury by MPTP, reasoning that when one system is “down,” others may increase function to compensate. In related tests in mice, he also found increases in an energy-stimulating cycle and in the mitochondrial transcript for tyrosine hydroxylase (TH), TH being the enzyme that converts the amino acid tyrosine into levodopa. Dr. Jakowec reports that the data derived from the studies resulted in a current RO1 NIH grant that he hopes will lead him to elaborate on the roles of both transmitter systems in order to identify new therapeutic targets aimed at the symptoms of neurodegenerative disorders such as PD.

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