Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson's disease.
Parkinson's disease (PD) is characterized by a progressive loss of substantia nigra pars compacta (SNc) neurons. The onset of clinical symptoms only occurs after the degeneration has exceeded a certain threshold. In most of the current 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) nonhuman primate models, nigrostriatal lesions and the onset of PD symptoms are the result of an immediate neuronal degeneration in the SNc caused by acute injection of the toxin. In order to develop a model that more closely mimics the degeneration pattern of human PD, we eventually established a protocol that produces a progressive parkinsonian state by treating monkeys repeatedly with MPTP for 15 +/- 2 d. Mean onset of parkinsonian symptoms occurred after 13.2 d of treatment. At this time, 56.8 +/- 6.3% of tyrosine hydroxylase immunoreactive neurons and 75.2 +/- 6.2% of Nissl-stained cells remained in the SNc. Striatal dopamine transporter (DAT) binding and dopamine (DA) content decreased to 19.7 +/- 4.9% and 18.2 +/- 5.6% of untreated monkeys. Parallel 123I-PEI single-photon emission computed tomography (SPECT) imaging in living animals showed a similar decrease in striatal DAT binding. In this article, we examine how this and other chronic MPTP models fit with human pathology.
Meissner
Wassilios
W
Basal Gang, Laboratoire de Neurophysiologie, CNRS UMR 5543, Université Victor Segalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Prunier
Caroline
C
Guilloteau
Denis
D
Chalon
Sylvie
S
Gross
Christian E
CE
Bezard
Erwan
E
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D008251:Macaca; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
D004298:Dopamine