Rapid ATP Loss Caused by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mouse Brain
Version of Record online: 5 OCT 2006
Journal of Neurochemistry
Volume 57, Issue 1, pages 348–351, July 1991
How to Cite
Chan, P., DeLanney, L. E., Irwin, I., Langston, J. W. and Di Monte, D. (1991), Rapid ATP Loss Caused by 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine in Mouse Brain. Journal of Neurochemistry, 57: 348–351. doi: 10.1111/j.1471-4159.1991.tb02134.x
- Issue online: 5 OCT 2006
- Version of Record online: 5 OCT 2006
- Received March 22, 1991; accepted March 26, 1991.
- Microwave irradiation
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.