Neuroprotective effects of pramipexole in young and aged MPTP-treated mice.
This study examined the effect of pramipexole (PPX), a selective dopamine (DA) D(3)/D(2) agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage to the nigrostriatal dopamine system in young (8-week-old) and aged (12-month-old) mice. Co-administration of PPX and MPTP to young or aged mice, followed by 2 or 14 days of additional PPX treatment, significantly attenuated MPTP-induced striatal DA loss. Pramipexole treatment also significantly attenuated the loss of tyrosine hydroxylase immunoreactive neurons (TH-IR) within the substantia nigra pars compacta (SNc) in both young and aged animals. Effects of PPX administration on dopaminergic cell survival were confirmed in Nissl-stained sections and by quantitation of retrogradely labeled Fluorogold-positive SNc neurons. Protective effects of PPX on striatal DA levels and SNc DA neuron survival were similar in young and aged animals, although the magnitude of these effects was significantly less in aged animals. These findings support the early initiation of PPX therapy in Parkinson's disease patients.
Anderson
D W
DW
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, 1020 Locust Street, JAH 521, Philadelphia, PA 19107, USA.
Neavin
T
T
Smith
J A
JA
Schneider
J S
JS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D052160:Benzothiazoles; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000077487:Pramipexole; D013266:Stilbamidines; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000978:Antiparkinson Agents; D052160:Benzothiazoles; D015259:Dopamine Agents; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D013266:Stilbamidines; D013844:Thiazoles; D000077487:Pramipexole; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine