Methamphetamine (METH) is an amphetamine analog that produces degeneration of the dopaminergic system in mammals. The neurotoxic effects of the drug are through to be mediated by oxygen-based free radicals. In the present report, we have used immortalized neural cells obtained from rat mesencephalon in order to further assess the role of oxidative stress in METH-induced neurotoxicity. We thus tested if the anti-death proto-oncogene, bcl-2, could protect against METH- induced cytotoxicity. METH caused dose-dependent loss of cellular viability in control cells while bcl-2-expressing cells were protected against these deleterious effects. Using flow cytometry, immunofluorescent staining, and DNA electrophoresis, we also show that METH exposure can cause DNA strand breaks, chromatin condensation, nuclear fragmentation and DNA laddering. All these changes were prevented by bcl-2 expression. These data indicate that METH exposure can cause cell death via an apoptotic process. Because DNA damage is associated with changes in the cell cycle, we sought to determine if METH could affect cell cycling. METH caused a marked decrease in the percentage of cells in the G1 phase. These observations provide further support for the involvement of oxidative stress in the toxic effects of amphetamine analogs. They also document that METH-induced cytotoxicity is secondary to apoptosis. These findings may be of relevance to the cause(s) of Parkinson's disease which involves degeneration of the nigrostriatal dopaminergic pathway.
| Jayanthi, S; Buie, S; Moore, S et al. (2010) Heavy marijuana users show increased serum apolipoprotein C-III levels: evidence from proteomic analyses. Mol Psychiatry 15:101-12 |
| Kalechstein, Ari D; De la Garza 2nd, Richard; Newton, Thomas F et al. (2009) Quantitative EEG abnormalities are associated with memory impairment in recently abstinent methamphetamine-dependent individuals. J Neuropsychiatry Clin Neurosci 21:254-8 |
| Flanagan, Jonathan M; Gerber, Alexandra L; Cadet, Jean Lud et al. (2006) The fatty acid amide hydrolase 385 A/A (P129T) variant: haplotype analysis of an ancient missense mutation and validation of risk for drug addiction. Hum Genet 120:581-8 |
| Cadet, Jean Lud; Bolla, Karen; Herning, Ronald I (2006) Neurological assessments of marijuana users. Methods Mol Med 123:255-68 |
| Matochik, John A; Eldreth, Dana A; Cadet, Jean-Lud et al. (2005) Altered brain tissue composition in heavy marijuana users. Drug Alcohol Depend 77:23-30 |
| Bolla, Karen I; Eldreth, Dana A; Matochik, John A et al. (2005) Neural substrates of faulty decision-making in abstinent marijuana users. Neuroimage 26:480-92 |
| Herning, Ronald I; Better, Warren E; Tate, Kimberly et al. (2005) Cerebrovascular perfusion in marijuana users during a month of monitored abstinence. Neurology 64:488-93 |
| Bolla, Karen; Ernst, Monique; Kiehl, Kent et al. (2004) Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci 16:456-64 |
| Radzius, Aleksandras; Gallo, Joseph; Gorelick, David et al. (2004) Nicotine dependence criteria of the DIS and DSM-III-R: a factor analysis. Nicotine Tob Res 6:303-8 |
| Bolla, K I; Eldreth, D A; London, E D et al. (2003) Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. Neuroimage 19:1085-94 |
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