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

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...

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Bibliographic Details
Published in:Canadian journal of neurological sciences 1992-02, Vol.19 (S1), p.124-133
Main Authors: Tatton, William G., Greenwood, Carol E., Seniuk, Nadine A., Salo, Paul T.
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Biological and medical sciences
Cell Death - drug effects
Cell Death - physiology
Disease Models, Animal
Humans
Medical sciences
Mice
MPTP Poisoning
Nervous system involvement in other diseases. Miscellaneous
Neurology
Neurons - drug effects
Neurons - physiology
Parkinson Disease - physiopathology
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Summary: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.
ISSN:0317-1671
2057-0155
DOI:10.1017/S0317167100041494