Acute and chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administrations elicit similar microglial activation in the substantia nigra of monkeys.
Increasing evidence suggests a pivotal role for neuroinflammation in the pathogenesis of Parkinson disease, but whether activated microglia participate in disease progression remains unclear. To clarify this issue, we determined the numbers of activated microglial cells in the substantia nigra pars compacta and ventral tegmental area of monkeys subacutely and chronically exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Monkeys in the subacute MPTP treatment group were killed 1 week after the last MPTP injection; chronically treated monkeys were killed either 6 or 35 months after the last MPTP injection. Subacute MPTP administration induced loss of dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area and microglial activation in the same areas. Chronic MPTP treatment resulted in greater dopaminergic neuron depletion in both treatment groups. Both groups of chronic MPTP-treated monkeys showed increased numbers of activated microglial cells in the substantia nigra pars compacta that were similar to those of the subacute MPTP treatment group. These results indicate that microglial activation seems to be induced mainly by the toxic effects of MPTP and that it does not further progress once the toxin administration has been terminated. This suggests that the progressive degeneration of nigral cells in Parkinson disease may not necessarily be associated with progressively increased microglial activation.
Vázquez-Claverie
Marianne
M
Laboratory of Regenerative Therapy, Department of Neurology and Neuroscience Division, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain.
Garrido-Gil
Pablo
P
San Sebastián
Waldy
W
Izal-Azcárate
Amaya
A
Belzunegui
Silvia
S
Marcilla
Irene
I
López
Berta
B
Luquin
María-Rosario
MR
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D020267:MPTP Poisoning / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D008252:Macaca fascicularis; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000008:administration & dosage; D013378:Substantia Nigra / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine