Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate

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

Autores

Sofia Baptista (Autor) Outra; Charlene Lasgi (Autor) Outra; Caroline Benstaali (Autor) Outra; Nuno Milhazes (Autor) Outra; Fernanda Borges (Autor) FCUP; Carlos Fontes Ribeiro (Autor) Outra; Fabienne Agasse (Autor) Outra; Ana Paula Silva (Autor) Outra

Revista

Título: Stem Cell Research

Vol. 13

ISSN: 1873-5061

Editora: Elsevier

Indexação

ISI Web of Knowledge - 10 Citações

Scopus - 9 Citações

Classificação Científica

FOS: Ciências da engenharia e tecnologias > Biotecnologia ambiental

CORDIS: Ciências da Saúde

Outras Informações

ID Authenticus: P-009-V56

Abstract (EN): Methamphetamine (METH) is a highly addictive psychostimulant drug of abuse that negatively interferes with neurogenesis. In fact, we have previously shown that METH triggers stem/progenitor cell death and decreases neuronal differentiation in the dentate gyrus (DG). Still, little is known regarding its effect on DG stem cell properties. Herein, we investigate the impact of METH on mice DG stem/progenitor cell self-renewal functions. METH (10 nM) decreased DG stem cell self-renewal, while 1 nM delayed cell cycle in the G0/G1-to-S phase transition and increased the number of quiescent cells (G0 phase), which correlated with a decrease in cyclin E, pEGFR and pERK1/2 protein levels. Importantly, both drug concentrations (1 or 10 nM) did not induce cell death. In accordance with the impairment of self-renewal capacity, METH (10 nM) decreased Sox2(+)/Sox2(+) while increased Sox2(-)/Sox2(-) pairs of daughter cells. This effect relied on N-methyl-D-aspartate (NMDA) signaling, which was prevented by the NMDA receptor antagonist, MK-801 (10 mu M). Moreover, METH (10 nM) increased doublecortin (DCX) protein levels consistent with neuronal differentiation. In conclusion, METH alters DG stem cell properties by delaying cell cycle and decreasing self-renewal capacities, mechanisms that may contribute to DG neurogenesis impairment followed by cognitive deficits verified in METH consumers. (C) 2014 The Authors. Published by Elsevier B. V.

Idioma: Inglês

Tipo (Avaliação Docente): Científica