title: Interactions between MPTP-induced and age-related neuronal death in a murine model of Parkinson's disease.
abstract: 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.
authors.affiliation: Center for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada.
authors.forename: W G
authors.initials: WG
authors.lastname: Tatton
authors.forename: C E
authors.initials: CE
authors.lastname: Greenwood
authors.forename: N A
authors.initials: NA
authors.lastname: Seniuk
authors.forename: P T
authors.initials: PT
authors.lastname: Salo
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D020267:MPTP Poisoning; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*