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Interactions Between MPTP-Induced and Age-Related Neuronal Death in a Murine Model of Parkinson’s Disease

Published online by Cambridge University Press:  18 September 2015

William G. Tatton ,
Carol E. Greenwood ,
Nadine A. Seniuk  and
Paul T. Salo
William G. Tatton*
Affiliation:
Center for Research in Neurodegenerative Diseases (W.G.T., N.A.S.)
Carol E. Greenwood
Affiliation:
Department of Physiology (W.G.T., P.T.S.)
Nadine A. Seniuk
Affiliation:
Department of Psychiatry (W.G.T.)
Paul T. Salo
Affiliation:
Department of Nutritional Sciences (C.E.G.), University of Toronto, Toronto
*
Center for Research in Neurodegenerative Diseases, Tanz Neuroscience Building, 6 Queens Park Crescent West, Toronto, Ontario, Canada M5S 1A8
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Abstract:

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Abiotrophy is hypothesized to explain the onset and time course of deficits in Parkinson’s disease (PD) Abiotrophy includes: 1) exposure to agent(s) causing the death of dopaminergic nigrostriatal neurons (DNSns), 2) gradual death of DNSns with age, 3) summation of 1) and 2) until DNSn numbers fall below a threshold for detectable neurological deficits. Murine DNSn death following methyl-phenyl-tetrahydropyridine (MPTP) exposure occurs according to an exponential relationship while age-related death of DNSns occurs according to a second exponential relationship. Summing the two exponential losses overestimates experimental DNSn death showing a simple abiotrophic model is not sufficient. Aged murine DNSns greatly increase their dopamine synthesis and the density of their striatal axon terminals which may explain the above threshold. Murine DNSns die gradually after MPTP exposure and L-deprenyl treatment rescues MPTP-damaged DNSns by a previously undiscovered action, altering the abiotrophic interactions and possibly explaining the slowed progression of PD found with deprenyl treatment.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 19 , Issue S1: 3rd Canadian Conference on Neurodegenerative Diseases , February 1992 , pp. 124 - 133
Copyright
Copyright © Canadian Neurological Sciences Federation 1992

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