Similarities and differences between MPTP-induced parkinsonsim and Parkinson's disease. Neuropathologic considerations.
The MPTP monkey model for PD has continued to display similarities as well as differences from the human disease, also in respect to its neuropathology. In 65 MPTP-treated squirrel monkeys with survival for more than 2 days, the main similarities consisted of nerve cell degeneration, not only of SN, but also, in the majority of cases, of the LC. In 13 animals that survived for from 1 to 7 years after their first exposure to MPTP, the nerve cells in the ventrolateral portion of the SN compacta were particularly vulnerable, just as in PD. The principal differences were the lack of progression of the disease process in these long-term animals (although this has yet to be systematically tested) and the absence of formation of typical Lewy bodies in the SN, LC, and other predilection sites for Lewy bodies. Since inclusion bodies, now observed in 16 monkeys, could be produced fairly consistently in aged MPTP-treated squirrel monkeys, they appeared to represent a bridge between these similarities and differences. They had some features, especially their location in predilection sites for Lewy bodies, such as the SN, in common with Lewy bodies, but did not display the fully convincing morphological and immunocytochemical features, characteristics of the human inclusion bodies in PD. Overall, these studies continue to provide tantalizing hints that this model could lead to important new insights into the pathologic process that underlies PD.
Forno
L S
LS
DVA Medical Center, Palo Alto, California 94304.
DeLanney
L E
LE
Irwin
I
I
Langston
J W
JW
D000818:Animals; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D006801:Humans; D002479:Inclusion Bodies / Q000187:drug effects / Q000648:ultrastructure; D016631:Lewy Bodies / Q000187:drug effects / Q000648:ultrastructure; D008125:Locus Coeruleus / Q000187:drug effects / Q000473:pathology; D020267:MPTP Poisoning; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology; D010300:Parkinson Disease / Q000473:pathology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology