Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Ema Alves (Author) Other; Teresa Summavielle (Author) Other; Cecilia Juliana Alves (Author) Other; Joana Gomes da Silva (Author) Other; Jose Custodio Barata (Author) Other; Eduarda Fernandes (Author) FFUP; Maria de Lourdes Bastos (Author) FFUP; Maria Amelia Tavares (Author) FMUP; Felix Carvalho (Author) FFUP

Journal

Title: Journal of Neuroscience

Vol. 27

Pages: 10203-10210

ISSN: 0270-6474

Publisher: Society for Neuroscience

Indexing

ISI Web of Knowledge - 55 Citations

Scopus - 66 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-004-7GE

DOI: 10.1523/jneurosci.2645-07.2007

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8