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Neuroprotective effects of MK-801 on l-2-chloropropionic acid-induced neurotoxicity.
- Source :
-
Journal of Neurochemistry . Feb2001, Vol. 76 Issue 4, p1057-1065. 9p. - Publication Year :
- 2001
-
Abstract
- l-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with l-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study aimed to investigate the effect of prior exposure to MK-801 on the biochemical and neurotoxicological effects of l-2-chloropropionic acid. Extracts were prepared from the forebrain and cerebellum of animals that had been treated with l-2-chloropropionic acid, with and without prior treatment with MK-801, and were analysed using magnetic resonance spectroscopy and amino acid analysis. Glucose metabolism was studied by monitoring the metabolism of [1-[sup 13]C]-glucose using GC/MS. l-2-Chloropropionic acid caused increased glucose metabolism in both brain regions 6 h after administration, confirming activation of the pyruvate dehydrogenase complex, which was not prevented by MK-801. After 48 h an increase in lactate and a decrease in N-acetylaspartate was observed only in the cerebellum, whereas phosphocreatine and ATP decreased in both tissues. MK-801 prevented the changes in lactate and N-acetylaspartate, but not those on the energy state. These studies suggest that l-2-chloropropionic acid-induced neurotoxicity is only partly mediated by the NMDA subtype of glutamate receptor. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CEREBELLUM
*NECROSIS
Subjects
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 76
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 5508467
- Full Text :
- https://doi.org/10.1046/j.1471-4159.2001.00104.x