MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Daniel J Jose Barbosa (Autor) Outra; Roman Serrat (Autor) Outra; Serena Mirra (Autor) Outra; Marti Quevedo (Autor) Outra; Elena G Gomez de Barreda (Autor) Outra; Jesus Avila (Autor) Outra; Eduarda Fernandes (Autor) FFUP; Maria de Lourdes Bastos (Autor) FFUP; Joao Paulo Capela (Autor) Outra; Felix Carvalho (Autor) FFUP; Eduardo Soriano (Autor) Outra

Revista

Título: Archives of Toxicology

Vol. 88

Páginas: 1561-1572

ISSN: 0340-5761

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 8 Citações

Scopus - 13 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-009-QQG

DOI: 10.1007/s00204-014-1209-7

Abstract (EN): Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related brain actions. We showed that MDMA dramatically reduced mitochondrial trafficking in hippocampal neurons in a Tau-dependent manner, in which glycogen synthase kinase 3 beta activity was implicated. Furthermore, we found that these trafficking abnormalities were rescued by over-expression of Mitofusin2 and dynamin-related protein 1, but not of Miro1. Given the relevance of mitochondrial targeting for neuronal function and neurotransmission, our data underscore a novel mechanism of action of MDMA that may contribute to our understanding of how this drug of abuse alters neuronal functioning.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12