The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain
The adult neural stem and progenitor cell niche is altered in amyotrophic lateral sclerosis mouse brain
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DOI：
10.1002/cne.21012
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发表时间：
2006-07-20
影响因子：
2.5
通讯作者：
Martin, Lee J.
中科院分区：
文献类型：
--
作者：
Liu, Zhiping;Martin, Lee J.
肌萎缩侧索硬化症（ALS）是一种由运动神经元变性引起的致命成人疾病。干细胞疗法可能是 ALS 的一种治疗方法。成年哺乳动物前脑在前脑室下区 (SVZa)、吻侧迁移流 (RMS)、嗅球 (OB) 核心和齿状回 (DG) 中具有神经干细胞 (NSC) 和神经祖细胞 (NPC)。这些细胞可通过内源性募集或自体/同种异体移植来拯救或替换退化的上运动神经元和下运动神经元。我们评估了携带人类突变型超氧化物歧化酶-1 (mSOD1)（一种 ALS 模型）的转基因 (tg) 小鼠中前脑 NSC 和 NPC 的能力。 Tg 人类野生型 SOD1 (wtSOD1) 小鼠和非 tg 小鼠为对照。细胞的溴脱氧尿苷 (BrdU) 标记是细胞增殖和其他事件的标记，在症状前和症状小鼠中以特定模式减少，其中 SVZa 的减少幅度大于 RMS、OB 和 DG。通过定位巢蛋白、神经细胞粘附分子、distalless-2 转录因子、波形蛋白和胶质纤维酸性蛋白来评估不同的 NSC 和 NPC 补体。在有症状的小鼠中，NSC 标记物减少，而 NPC 标记物未改变或升高。有症状的 mSOD1 小鼠的神经发生得以保留。 NSC/NPC 体外能力评估显示，mSOD1 SVZa 细胞具有增殖和形成神经球的能力，但对丝裂原刺激的反应受损。我们得出的结论是，成年 mSOD1 ALS 小鼠的前脑 NSC 存在异常，但 NSC/NPC 的基本特征在症状前和症状小鼠中仍然存在。
Amyotrophic lateral sclerosis (ALS) is a fatal adult human disease caused by motor neuron degeneration. Stem cell therapy might be a treatment for ALS. The adult mammalian forebrain has neural stem cells (NSCs) and neural progenitor cells (NPCs) in the anterior subventricular zone (SVZa), rostral migratory stream (RMS), olfactory bulb (OB) core, and dentate gyrus (DG). These cells could be used to rescue or replace degenerating upper and lower motor neurons through endogenous recruitment or autologous/allogenic transplantation. We evaluated the competency of forebrain NSCs and NPCs in transgenic (tg) mice harboring human mutant superoxide dismutase-1 (mSOD1), a model of ALS. Tg human wild-type SOD1 (wtSOD1) mice and non-tg mice were controls. Bromodeoxyuridine (BrdU) labeling of cells, a marker for cell proliferation and other events, was reduced in a niche-specific pattern in presymptomatic and symptomatic mice, with the SVZa having greater reductions than the RMS, OB, and DG. Different NSC and NPC complements were evaluated by localizing nestin, neural cell adhesion molecule, distalless-2 transcription factor, vimentin, and glial fibrillary acidic protein. In symptomatic mice, NSC markers were reduced, whereas NPC markers were unchanged or elevated. Neurogenesis was preserved in symptomatic mSOD1 mice. NSC/NPC competence assessment in vitro revealed that mSOD1 SVZa cells had the ability to proliferate and form neurospheres but had an impaired response to mitogen stimulation. We conclude that adult mSOD1 ALS mice have abnormalities in forebrain NSCs, but the essential features of NSC/NPCs remained in presymptomatic and symptomatic mice.