کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2590167 1131727 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biphasic mechanism of the toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) as revealed by dynamic changes in glucose metabolism in rat brain slices
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Biphasic mechanism of the toxicity induced by 1-methyl-4-phenylpyridinium ion (MPP+) as revealed by dynamic changes in glucose metabolism in rat brain slices
چکیده انگلیسی

1-Methyl-4-phenylpyridinium (MPP+) is a well-known neurotoxin which causes a clinical syndrome similar to Parkinson's disease. The classical mechanism of MPP+ toxicity involves its entry into cells through the dopamine transporter (DAT) to inhibit aerobic glucose metabolism, while recent studies suggest that an oxidative mechanism may contribute to the toxicity of MPP+. However, it has not been adequately determined what role these two mechanisms play in the development of neurotoxicity after MPP+ loading in the brain. To clarify this issue, MPP+ was added directly to fresh rat brain slices and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) produced by MPP+ were serially and two-dimensionally measured using the dynamic positron autoradiography technique with [18F]2-fluoro-2-deoxy-d-glucose as a tracer. MPP+ dose-dependently increased CMRglc in each of the brain regions examined, reflecting enhanced glycolysis compensating for the decrease in aerobic metabolism. Treatment with DAT inhibitor GBR 12909 significantly attenuated the enhanced glycolysis induced by 10 μM MPP+ in the striatum. Treatment with free radical spin trap α-phenyl-N-tert-butylnitrone (PBN) significantly attenuated the enhancement of glycolysis induced by 100 μM MPP+ in all brain regions. These results suggest that the mechanism of the toxicity of MPP+ is biphasic and consists of a DAT-mediated mechanism selective for dopaminergic regions at a lower concentration of MPP+ (10 μM), and an oxidative mechanism that occurs at a higher concentration of MPP+ (100 μM) and is not restricted to dopaminergic regions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: NeuroToxicology - Volume 28, Issue 3, May 2007, Pages 672–678
نویسندگان
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