Parallel increases in lipid and protein oxidative markers in several mousebrain regions after methamphetamine treatment

Citation
Mr. Gluck et al., Parallel increases in lipid and protein oxidative markers in several mousebrain regions after methamphetamine treatment, J NEUROCHEM, 79(1), 2001, pp. 152-160
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
79
Issue
1
Year of publication
2001
Pages
152 - 160
Database
ISI
SICI code
0022-3042(200110)79:1<152:PIILAP>2.0.ZU;2-U
Abstract
The neurotoxic actions of methamphetamine (METH) may be mediated in part by reactive oxygen species (ROS). Methamphetamine administration leads to inc reases in ROS formation and lipid peroxidation in rodent brain; however, th e extent to which proteins may be modified or whether affected brain region s exhibit similar elevations of lipid and protein oxidative markers have no t been investigated. In this study we measured concentrations of TBARs, pro tein 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). Sub stantial increases in TBARs and protein carbonyls were observed in the stri atum 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 elevat ions in oxidative markers were significantly greater at 24 h than at 4 h. M onoamine levels were maximally reduced within 4 h (striatal dopamine [DA] b y 95% and serotonin [5-HT] in striatum, cortex and hippocampus by 60-90%). These decrements persisted for 7 days after METH, indicating effects reflec tive of nerve terminal damage. Interestingly, NE was only transiently deple ted in the brain regions investigated (hippocampus and cortex), suggesting a pharmacological and non-toxic action of METH on the noradrenergic nerve t erminals. This study provides the first evidence for concurrent formation o f lipid and protein markers of oxidative stress in several brain regions of mice that are severely affected by large neurotoxic doses of METH. Moreove r, the differential time course for monoamine depletion and the elevations in oxidative markers indicate that the source of oxidative stress is not de rived directly from DA or 5-HT oxidation.