Rapid ATP Loss Caused by 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Mouse Brain

Rapid ATP Loss Caused by 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Mouse Brain Abstract: The effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) on ATP levels in different areas of mouse brain were studied after rapid fixation of cerebral tissue in situ by microwave irradiation. ATP levels in the striatum, ventral mesencephalon, and cerebellum of untreated C57BL/6 mice killed by microwave irradiation were 2‐3 times greater than values measured in the brains of animals killed by cervical dislocation. In microwaved mice, administration of MPTP (40 mg/kg s.c.) caused a 10‐20% decrease in ATP concentrations as compared to control animals injected with saline. This decrease was relatively rapid and selective because it occurred in both the striatum and ventral mesencephalon, but not in the cerebellar and frontal cortex, at 30, 60, 120, and 240 min after MPTP exposure. Furthermore, ATP loss in the striatum was prevented by mazindol, a catecholamine uptake blocker, indicating a rather selective effect of MPTP on the ATP content of dopaminergic terminals. Results of this study are consistent with mitochondrial damage in the MPTP model of parkinsonism and provide the first direct experimental evidence in vivo that a decrease in ATP may play a role in MPTP‐induced neurotoxicity. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Rapid ATP Loss Caused by 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Mouse Brain

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Publisher
Wiley
Copyright
Copyright © 1991 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1991.tb02134.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: The effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) on ATP levels in different areas of mouse brain were studied after rapid fixation of cerebral tissue in situ by microwave irradiation. ATP levels in the striatum, ventral mesencephalon, and cerebellum of untreated C57BL/6 mice killed by microwave irradiation were 2‐3 times greater than values measured in the brains of animals killed by cervical dislocation. In microwaved mice, administration of MPTP (40 mg/kg s.c.) caused a 10‐20% decrease in ATP concentrations as compared to control animals injected with saline. This decrease was relatively rapid and selective because it occurred in both the striatum and ventral mesencephalon, but not in the cerebellar and frontal cortex, at 30, 60, 120, and 240 min after MPTP exposure. Furthermore, ATP loss in the striatum was prevented by mazindol, a catecholamine uptake blocker, indicating a rather selective effect of MPTP on the ATP content of dopaminergic terminals. Results of this study are consistent with mitochondrial damage in the MPTP model of parkinsonism and provide the first direct experimental evidence in vivo that a decrease in ATP may play a role in MPTP‐induced neurotoxicity.

Journal

Journal of NeurochemistryWiley

Published: Jul 1, 1991

References

  • Mitochondrial complex I deficiency in Parkinson's disease
    Schapira, Schapira; Cooper, Cooper; Dexter, Dexter; Clark, Clark; Jenner, Jenner; Marsden, Marsden

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