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At least 2 decades have past since the demonstration of a 40-50% deficit in total glutathione (GSH) levels in the substantia nigra in patients with Parkinson's disease (PD). The similar loss of GSH in the nigra in Incidental Lewy body disease, thought to be an early form of PD, indicates that this is one of the earliest derangements to occur in the(More)
The mechanisms involved in methamphetamine (METH)-induced damage to nigrostriatal dopaminergic neurons in experimental animals are unknown. We have examined the possibility that perturbations in energy metabolism contribute to METH-induced toxicity by investigating the effects of systemic METH treatment in mice which received a unilateral intrastriatal(More)
The effects of different severities of metabolic stress on dopamine (DA) and gamma-aminobutyric acid (GABA) cell loss were examined in rat mesencephalic culture. Partial metabolic inhibition was induced in 12-day-old cultures by a 24-hr treatment with various concentrations of 3-nitropropionic acid(3-NPA, 0.1-0.5 mM) or malonate (10-50 mM), irreversible and(More)
Defects in mitochondrial energy metabolism have been implicated in the pathology of several neurodegenerative disorders. In addition, the reactive metabolites generated from the metabolism and oxidation of the neurotransmitter dopamine (DA) are thought to contribute to the damage to neurons of the basal ganglia. We have previously demonstrated that(More)
Recent studies suggest that exposure to agrochemicals may contribute to the development of idiopathic Parkinson's disease. Maneb (MB), a widely used Mn-containing ethylene-bis-dithiocarbamate (EBDC) fungicide, has been implicated in selective dopaminergic neurotoxicity. In this study, we examine the potential neurotoxicity of mancozeb (MZ), a widely used(More)
"Graded" metabolic stress was induced chemically in an ex vivo preparation of retina to examine the early events following metabolic inhibition that lead to acute toxicity. Toxicity was assessed histologically and by quantitation of endogenous gamma-aminobutyric acid (GABA) release. Blockade of glycolysis with iodoacetate or electron transport with(More)
Parkinson's disease (PD) is associated with loss of total glutathione (GSH) which may contribute to progressive cell death. Peripheral GSH administration has been used clinically with reported benefits. Despite this, there is little specific information to characterize its cellular uptake or clearance, brain elevation with peripheral delivery or(More)
Although controversial, studies with methamphetamine and MPTP suggest a link between glutamate-mediated excitotoxicity and degeneration of dopamine cells. Both compounds are thought to create a metabolic stress. To further explore glutamate actions in DA degeneration, we investigated the effects of other metabolic inhibitors. In mesencephalic cultures, DA(More)
Glutamate (Glu) and its receptors are involved in the maturation and maintenance of the neural mechanisms governing the preovulatory LH surge of young, reproductive-aged rodents and nonhuman primates. Little is known about the role of Glu in the delayed onset and reduced peak amplitude of the LH surge that characterizes female rodents during early(More)
The effect of the endonuclease inhibitor aurintricarboxylic acid (ATA) versus NMDA-mediated delayed cell death was examined in an ex vivo chick retinal preparation. Transient exposure to 100 microM NMDA for 60 min followed by a 24-h recovery period resulted in a sevenfold increase in lactate dehydrogenase (LDH) release into the medium. ATA at 100 microM(More)