The effect of methamphetamine on subventricular zone neurogenesis: Cell death, proliferation and differentiation

Abstract

Methamphetamine (METH) is a potent and widely consumed psychostimulant which causes brain functional and structural abnormalities. However, little is known about the effect of METH on adult neurogenic niches and its consequences on the subventricular zone (SVZ). Thus, this work aims to disclose the effects of METH on SVZ neurogenesis. SVZ neurospheres were cultured from early postnatal mice and subjected to increasing concentrations of METH (1 μM to 500 μM). After 24 hours of exposure to METH cell death was triggered by both necrosis and apoptosis. METH exerted toxic effects on stem/progenitor cells expressing SOX2, but not on doublecortin-labeled neuroblasts. METH decreased BrdU incorporation in SVZ cell cultures. Furthermore, METH decreased the number of NeuN-positive neurons, as well as P-JNK-positive growing axons. Altogether, our data demonstrate that METH is toxic to SVZ cells and reduces neuronal differentiation and maturation at non toxic concentrations.