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

A. R. Bento, S. Baptista, J. Malva, A. P. Silva, F. Agasse
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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.
甲基苯丙胺对脑室下区神经发生的影响:细胞死亡、增殖和分化
甲基苯丙胺是一种广泛使用的强效精神兴奋剂,可导致大脑功能和结构异常。然而,甲基安非他明对成人神经源性壁龛的影响及其对心室下区(SVZ)的影响知之甚少。因此,本研究旨在揭示甲基安非他明对SVZ神经发生的影响。从出生后早期小鼠中培养SVZ神经球,并增加甲基安非他明浓度(1 μM至500 μM)。暴露于甲基安非他明24小时后,细胞以坏死和凋亡两种方式死亡。甲基苯丙胺对表达SOX2的干细胞/祖细胞有毒性作用,但对双皮质素标记的神经母细胞没有毒性作用。甲基安非他明降低SVZ细胞培养中BrdU的掺入。此外,甲基安非他明减少了neun阳性神经元的数量,以及p - jnk阳性生长轴突的数量。总之,我们的数据表明,甲基安非他明对SVZ细胞是有毒的,并且在无毒浓度下会减少神经元的分化和成熟。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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