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Title: Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate
Authors: Baptista, Sofia 
Lasgi, Charlène 
Benstaali, Caroline 
Milhazes, Nuno 
Borges, Fernanda 
Fontes-Ribeiro, Carlos 
Agasse, Fabienne 
Silva, Ana Paula 
Issue Date: Sep-2014
Publisher: Elsevier
Citation: BAPTISTA, Sofia [et. al] - Methamphetamine decreases dentate gyrus stem cell self-renewal and shifts the differentiation towards neuronal fate. "Stem Cell Research". ISSN 1873-5061. Vol. 13 Nº. 2 (2014) p. 329–341
Serial title, monograph or event: Stem Cell Research
Volume: 13
Issue: 2
Abstract: 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 μM). 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.
ISSN: 1873-5061
DOI: 10.1016/j.scr.2014.08.003
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
I&D IBILI - Artigos em Revistas Internacionais

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