PMID- 17881526 OWN - NLM STAT- MEDLINE DCOM- 20071011 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 27 IP - 38 DP - 2007 Sep 19 TI - Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria. PG - 10203-10 AB - 3,4-Methylenedioxymethamphetamine (MDMA)-induced neurotoxicity and the protective role of monoamine oxidase-B (MAO-B) inhibition were evaluated at the mitochondrial level in various regions of the adolescent rat brain. Four groups of adolescent male Wistar rats were used: (1) saline control, (2) exposed to MDMA (4 x 10 mg/kg, i.p.; two hourly), (3) treated with selegiline (2 mg/kg, i.p.) 30 min before the same dosing of MDMA, and (4) treated with selegiline (2 mg/kg, i.p.). Body temperatures were monitored throughout the whole experiment. Animals were killed 2 weeks later, and mitochondria were isolated from several brain regions. Our results showed that "binge" MDMA administration causes, along with sustained hyperthermia, long-term alterations in brain mitochondria as evidenced by increased levels of lipid peroxides and protein carbonyls. Additionally, analysis of mitochondrial DNA (mtDNA) revealed that NDI nicotinamide adenine dinucleotide phosphate dehydrogenase subunit I and NDII (nicotinamide adenine dinucleotide phosphate dehydrogenase subunit II) subunits of mitochondrial complex I and cytochrome c oxidase subunit I of complex IV suffered deletions in MDMA-exposed animals. Inhibition of MAO-B by selegiline did not reduce hyperthermia but reversed MDMA-induced effects in the oxidative stress markers, mtDNA, and related protein expression. These results indicate that monoamine oxidation by MAO-B with subsequent mitochondrial damage may be an important contributing factor for MDMA-induced neurotoxicity. FAU - Alves, Ema AU - Alves E AD - Neurobehaviour Unit, Instituto de Biologia Molecular e Celular, Medical School of Porto, University of Porto, 4099-002 Porto, Portugal. FAU - Summavielle, Teresa AU - Summavielle T FAU - Alves, Cecilia Juliana AU - Alves CJ FAU - Gomes-da-Silva, Joana AU - Gomes-da-Silva J FAU - Barata, Jose Custodio AU - Barata JC FAU - Fernandes, Eduarda AU - Fernandes E FAU - Bastos, Maria de Lourdes AU - Bastos Mde L FAU - Tavares, Maria Amelia AU - Tavares MA FAU - Carvalho, Felix AU - Carvalho F LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Monoamine Oxidase Inhibitors) RN - EC 1.4.3.4 (Monoamine Oxidase) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Age Factors MH - Animals MH - Brain/drug effects/*enzymology MH - Lipid Peroxidation/drug effects/physiology MH - Male MH - Mitochondria/drug effects/*enzymology MH - Monoamine Oxidase/*metabolism MH - Monoamine Oxidase Inhibitors/pharmacology MH - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity MH - Neurotoxicity Syndromes/enzymology MH - Rats MH - Rats, Wistar PMC - PMC6672671 EDAT- 2007/09/21 09:00 MHDA- 2007/10/12 09:00 PMCR- 2008/03/19 CRDT- 2007/09/21 09:00 PHST- 2007/09/21 09:00 [pubmed] PHST- 2007/10/12 09:00 [medline] PHST- 2007/09/21 09:00 [entrez] PHST- 2008/03/19 00:00 [pmc-release] AID - 27/38/10203 [pii] AID - 3258663 [pii] AID - 10.1523/JNEUROSCI.2645-07.2007 [doi] PST - ppublish SO - J Neurosci. 2007 Sep 19;27(38):10203-10. doi: 10.1523/JNEUROSCI.2645-07.2007.