Neural progenitor cells are protected against MPTP by MAO-B inhibitors
Neural progenitor cells are protected against MPTP by MAO-B inhibitors
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DOI：
10.1016/j.neuro.2008.05.009
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发表时间：
2008-11-01
期刊：
影响因子：
3.4
通讯作者：
Nakayama, Hiroyuki
中科院分区：
文献类型：
--
作者：
He, Xi Jun;Uetsuka, Koji;Nakayama, Hiroyuki
MPTP对黑质纹状体多巴胺能系统的神经毒性作用被认为是由1-甲基-4-苯基吡啶（MPP+）引发的，MPP+是由单胺氧化酶（MAO）-B介导的MPTP氧化形成的代谢物。我们以前报道，管理MPTP诱导凋亡迁移成神经细胞（神经祖细胞，NPC）在成年小鼠。为了确定MAO-B是否也参与MPTP对NPC的神经毒性，本研究观察了MAO B抑制剂R（-）-丙炔苯丙胺（丙炔苯丙胺）和N-（2-氨乙基）-4-氯苯甲酰胺（Ro 16-6491）的作用，这两种药物都能保护多巴胺能系统免受MPTP的侵害。在盐水或MAO-B抑制剂处理的动物中发现很少有凋亡细胞，但MPTP在1天后显着诱导室下区（SVZ）和吻侧移行流（RMS）的凋亡。当小鼠用丙炔苯丙胺或Ro 16-6491预处理时，不仅黑质纹状体多巴胺水平，而且NPC也显着保护MPTP。此外，MPTP诱导的细胞凋亡被发现在青少年（出生后21天）和老年人（12个月大）的小鼠，这表明NPC是不同的多巴胺系统，已被认为表现出年龄依赖性的易感性MPTP。(C)2008年爱思唯尔公司All rights reserved.
Neurotoxic effects of MPTP on the nigrostriatal dopaminergic system are thought to be initiated by 1-methyl-4-phenylpyridinium (MPP+), a metabolite formed by the monoamine oxidase (MAO)-B-mediated oxidation of MPTP. We previously reported that the administration of MPTP induced apoptosis in migrating neuroblasts (neural progenitor cells, NPCs) in adult mice. To determine whether MAO-B is also involved in the neurotoxicity of MPTP to NPCs, this study looked at the effects of MAO B inhibitors, R(-)-deprenyl (deprenyl) and N-(2-aminoethyl)-4-chlorobenzamide (Ro 16-6491), both of which protect the dopaminergic system against MPTP. Few apoptotic cells were found in saline- or MAO-B inhibitor-treated animals but MPTP markedly induced apoptosis in the subventricular zone (SVZ) and rostral migratory stream (RMS) after 1 day. When mice were pretreated with deprenyl or Ro 16-6491, not only nigrostriatal dopamine levels but also NPCs were significantly protected against MPTP. In addition, MPTP-induced apoptosis was found in both juvenile (postnatal 21 days) and older (12 months old) mice, suggesting NPCs to be different from the dopamine system, which has been thought to exhibit age-dependent susceptibility to MPTP. (C) 2008 Elsevier Inc. All rights reserved.