title: Cocaine-induced oxidative stress precedes cell death in human neuronal progenitor cells.
abstract: By 2003, an estimated 34 million Americans had used cocaine according to the National Survey on Drug Use & Health. About 5.9 million of those had used in the past 12 months. Chronic cocaine users often develop addiction, dependency and tolerance to the drug. The psychological and physical effects of cocaine are due to the disruption of the limbic system in the central nervous system (CNS). Increased oxidative stress reported in the frontal cortex and the striatum of rats exposed to cocaine suggests that oxidative damage plays a significant role in cocaine-induced disruption of the CNS. Although it is evident that cocaine induces oxidative stress in the CNS, little has been learned about whether such increased oxidative stress is also relevant to apoptosis in cocaine-exposed models. To gain insight into the role of cocaine-induced oxidative stress in apoptosis, we hypothesized that oxidative stress precedes cell death when cocaine is administrated. To test this hypothesis, we have monitored the oxidative stress and apoptotic effects of acute cocaine exposure in human neuronal progenitor cells (HNPC). We found that oxidative stress was significantly increased at 48h after a 30min cocaine exposure compared to control cells, and that this was followed by cell death at 72h. Using the same experimental paradigm we have previously shown that pro-inflammatory genes are up-regulated in cocaine-exposed HNPC at 24h. Therefore, we suggest that the increased oxidative stress (possibly mediated by inflammatory responses) precedes cell death in cocaine-exposed HNPC. This may have implications for the consequences of cocaine abuse in situations where antioxidant capacity is compromised, as in the aging brain.
authors.affiliation: Roskamp Institute, 2040 Whitfield Ave., Sarasota, FL 34243, United States. fpoon@rfdn.org
authors.forename: H Fai
authors.initials: HF
authors.lastname: Poon
authors.forename: Laila
authors.initials: L
authors.lastname: Abdullah
authors.forename: Myles A
authors.initials: MA
authors.lastname: Mullan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mullan
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Crawford
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D003042:Cocaine / Q000494:pharmacology*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D003042:Cocaine