Neuroprotective effects of pramipexole in young and aged MPTP-treated mice

• Published in: Brain research Vol. 905; no. 1; pp. 44 - 53
• Main Authors: Anderson, David W, Neavin, T, Smith, J.A, Schneider, J.S
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 29.06.2001; Amsterdam Elsevier; New York, NY
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Aging - drug effects; Aging - physiology; Animals; Antiparkinson Agents - pharmacology; Benzothiazoles; Biological and medical sciences; Cell survival; Cell Survival - drug effects; Cell Survival - physiology; Dopamine; Dopamine - metabolism; Dopamine Agents - pharmacology; Fluorescent Dyes - pharmacokinetics; Immunohistochemistry; Male; Medical sciences; Mice; Mice, Inbred C57BL; MPTP; Neostriatum - drug effects; Neostriatum - pathology; Neostriatum - physiopathology; Neural Pathways - drug effects; Neural Pathways - pathology; Neural Pathways - physiopathology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuropharmacology; Neuroprotection; Neuroprotective agent; Neuroprotective Agents - pharmacology; Neurorestoration; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - pathology; Parkinsonian Disorders - physiopathology; Parkinson’s disease; Pharmacology. Drug treatments; PPX; Pramipexole; Stilbamidines; Substantia Nigra - drug effects; Substantia Nigra - pathology; Substantia Nigra - physiopathology; Thiazoles - pharmacology; Tyrosine 3-Monooxygenase - metabolism; Disorders of the nervous system; Neuroprotection; Dopamine; Cell survival; Neurorestoration; PPX; MPTP; Parkinson’s disease; Nervous system diseases; Rodentia; Parkinson disease; Neuroprotective agent; Catecholamine; Pramipexole; Cerebral disorder; Toxin; Vertebrata; Mammalia; Mouse; Animal; Central nervous system disease; Neurotoxin; Neurotransmitter; Degenerative disease; Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02466-0

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.