Journal ArticleDOI
In vivo trapping of hydroxyl free radicals in the striatum utilizing intracranial microdialysis perfusion of salicylate: effects of MPTP, MPDP+, and MPP+.
T. Obata,Chuang C. Chiueh +1 more
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In this paper, the authors demonstrated that sustained elevation of dopamine in extracellular fluid elicited by MPTP analogues can lead to the formation of cytotoxic free radicals near the nigrostriatal terminals.Abstract:
Increased formation of hydroxyl free radicals (·OH) reflected by ·OH adduct of salicylate in brain dialysate was demonstrated during the sustained (more than 2 hours) dopamine overflow elicited by 75 nmol of 1-methyl-4-phenyldihydropyridine (MPDP+) and 1-methyl-4-phenylpyridinium (MPP+) in the rat striatum. Owing to its weak dopamine releasing action, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did not significantly increase the ·OH formation. This data suggests that sustained elevation of dopamine in the extracellular fluid elicited by MPTP analogues can be auto-oxidized, which in turn leads (possibly by indirect mechanisms) to the formation of cytotoxic ·OH free radicals near the nigrostriatal terminals.read more
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Neuroprotection by the Metabolic Antioxidant α-Lipoic Acid
TL;DR: It is proposed that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues.
Journal ArticleDOI
Animal models of Parkinson's disease: an empirical comparison with the phenomenology of the disease in man.
Manfred Gerlach,Peter Riederer +1 more
TL;DR: The present contribution starts out by describing some of the clinical, pathological and neurochemical phenomena of Parkinson's disease, and hypotheses concerning the mechanisms of these neurotoxines have been related to the pathogenesis of nigral cell death in PD.
Journal ArticleDOI
Distinct Mechanisms Underlie Neurotoxin-Mediated Cell Death in Cultured Dopaminergic Neurons
TL;DR: Significant, dose-dependent levels of protection were seen in these in vitro models of PD using the C3 carboxyfullerene derivative, whereas it only partially rescued dopaminergic neurons from MPP+-induced cell death.
Journal ArticleDOI
MPTP mouse models of Parkinson's disease: an update.
TL;DR: The ability of MPTP mouse models to replicate the pathophysiology of PD, the mechanisms ofMPTP-induced neurotoxicity, strain differences in susceptibility to MPTP, and the models' roles in testing therapeutic approaches are discussed.
Journal ArticleDOI
The parkinsonism-inducing drug 1-methyl-4-phenylpyridinium triggers intracellular dopamine oxidation. A novel mechanism of toxicity.
TL;DR: The results suggest that in the presence of a Complex I defect, misregulation of DA storage could lead to the loss of nigrostriatal neurons in Parkinson's disease.
References
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The Rat Brain in Stereotaxic Coordinates
George Paxinos,Charles Watson +1 more
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
Journal ArticleDOI
Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains.
Peter Riederer,Emin Sofic,Wolf-Dieter Rausch,Bruno Schmidt,Gavin P. Reynolds,Kurt A. Jellinger,Moussa B.H. Youdim +6 more
TL;DR: Reduced glutathione and the shift of the iron (II)/iron (III) ratio in favor of iron ( III) suggest that these changes might contribute to pathophysiological processes underlying PD.
Journal ArticleDOI
Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease
D. Dexter,C.J. Carter,F. R. Wells,F. Javoy-Agid,Yves Agid,Andrew J. Lees,Peter Jenner,C. D. Marsden +7 more
TL;DR: The results may indicate that an increased level of lipid peroxidation continues to occur in the parkinsonian nigra up to the time of death, perhaps because of continued exposure to excess free radicals derived from some endogenous or exogenous neurotoxic species.
Journal ArticleDOI
The effect of age on the non-haemin iron in the human brain.
B Hallgren,P Sourander +1 more
TL;DR: The most extensive and systematic investigations of histologically demonstrable iron in the brain were conducted by SPATZ (1922), which found a fine granular deposit of iron in individual oligodendroglia cells and nerve cells, mainly in the globus pallidus and in the red zone of substantia nigra.
Journal ArticleDOI
Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease
TL;DR: Quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains demonstrates that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neurmelan in-pIGmented neurons they contain, and suggests a selective vulnerability of the neuromelsin- pigmented subpopulation of dopamine- containing mesencephalic neurons in Parkinson's disease.