Parallel increases in lipid and protein oxidative markers in several mouse brain regions after methamphetamine treatment
Article first published online: 7 JUL 2008
Journal of Neurochemistry
Volume 79, Issue 1, pages 152–160, October 2001
How to Cite
Gluck, M. R., Moy, L. Y., Jayatilleke, E., Hogan, K. A., Manzino, L. and Sonsalla, P. K. (2001), Parallel increases in lipid and protein oxidative markers in several mouse brain regions after methamphetamine treatment. Journal of Neurochemistry, 79: 152–160. doi: 10.1046/j.1471-4159.2001.00549.x
- Issue published online: 7 JUL 2008
- Article first published online: 7 JUL 2008
- Received June 5, 2001; revised manuscript received July 19, 2001; accepted July 19, 2001.
- protein carbonyls;
The neurotoxic actions of methamphetamine (METH) may be mediated in part by reactive oxygen species (ROS). Methamphetamine administration leads to increases in ROS formation and lipid peroxidation in rodent brain; however, the extent to which proteins may be modified or whether affected brain regions exhibit similar elevations of lipid and protein oxidative markers have not been investigated. In this study we measured concentrations of TBARs, protein carbonyls and monoamines in various mouse brain regions at 4 h and 24 h after the last of four injections of METH (10 mg/kg/injection q 2 h). Substantial increases in TBARs and protein carbonyls were observed in the striatum and hippocampus but not the frontal cortex nor the cerebellum of METH-treated mice. Furthermore, lipid and protein oxidative markers were highly correlated within each brain region. In the hippocampus and striatum elevations in oxidative markers were significantly greater at 24 h than at 4 h. Monoamine levels were maximally reduced within 4 h (striatal dopamine [DA] by 95% and serotonin [5-HT] in striatum, cortex and hippocampus by 60–90%). These decrements persisted for 7 days after METH, indicating effects reflective of nerve terminal damage. Interestingly, NE was only transiently depleted in the brain regions investigated (hippocampus and cortex), suggesting a pharmacological and non-toxic action of METH on the noradrenergic nerve terminals. This study provides the first evidence for concurrent formation of lipid and protein markers of oxidative stress in several brain regions of mice that are severely affected by large neurotoxic doses of METH. Moreover, the differential time course for monoamine depletion and the elevations in oxidative markers indicate that the source of oxidative stress is not derived directly from DA or 5HT oxidation.