Michael Kirby mkirby at vt.edu
Sun Nov 24 14:26:33 EST 1996

Dr. Jeffrey Bloomquist, Dr. Neal Castagnoli, Jr. and Michael Kirby are
working specifically on this question.  In fact they are the only ones
working on this particular aspect of parkinsonism (no other posters or
papers for the last 3 years at either the Society for Neuroscience or
Society of Toxicology annual meetings-- also, no other studies in the
current literature).  Their work, mostly Bloomquist and Kirby, concerns
changes in striatal neurochemistry following exposure to organochlorines
(spec. cyclodienes).  Their work was recently presented at the Society for
Neuroscience annual meeting in Washington, DC (last week).  We found that
subchronic exposure of C57BL/6 retired breeder mice to heptachlor causes
both a 2-3 fold increase in Vmax of dopamine uptake and a 4-5 fold
increase in dopamine uptake transporter expression as verified by
immunochemistry (complements of Gary Miller, Emory).  We postulate that
these conditions could sensitize individuals to other environmental agents
whose selectivity for the nigrostriatal tract is based upon utilization of
dopamine uptake transporters (e.g., MPP+, perhaps betacarbolines or
tetraisoquinolines, or other unknown agents).  Also, the condition
produced in the terminals themselves could predispose neurons to damage in
that (as per the paper):  cyclodienes cause presynaptic depletion of
transmitter stores by an as yet unknown mechanism, and are GABAa
antagonists.  Both of these conditions would be phsyiologically
synergistic in vivo and could result in a respectable degree of neuronal
stress.  Upcoming studies will emphasize effects of organophosphates on
striatal neurochemistry in treated animals and in vitro pharmacology of
the striatum with OPs.  Hope this helps.

Michael Kirby
Virginia Polytechnic Inst.
mkirby at vt.edu

Michael Kirby
mkirby at vt.edu

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