Temporal response of neural progenitor cells to disease onset and progression in amyotrophic lateral sclerosis-like Transgenic mice
Temporal response of neural progenitor cells to disease onset and progression in amyotrophic lateral sclerosis-like Transgenic mice
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DOI：
10.1089/scd.2006.0120
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发表时间：
2007-08-01
影响因子：
4
通讯作者：
Liu, Rugao
中科院分区：
文献类型：
--
作者：
Chi, Liying;Gan, Li;Liu, Rugao
通过神经干细胞（NSCs）或神经祖细胞（NPCs）的再生医学已被提出作为肌萎缩侧索硬化症（ALS）神经功能障碍恢复的替代途径。在再生医学可应用于ALS治疗之前，了解内源性成体NPC对运动神经元变性的反应的组织和分布是至关重要的。出于这个原因，我们使用巢蛋白增强子驱动的LacZ报告基因转基因小鼠（pNes-Tg小鼠，对照）和含有巢蛋白增强子驱动的LacZ报告基因和突变型G93 A-SOD 1基因的双转基因小鼠（Bi-Tg小鼠）分析了NPC对脊髓和脑中运动神经元变性的时间响应。与年龄匹配的pNes-Tg对照小鼠相比，我们观察到Bi-Tg小鼠在疾病发作和进展阶段脊髓背角中的NPC增加。相反，在疾病进展阶段检测到腹角中的NPC增加。另一方面，在疾病发作阶段检测到运动皮层中的NPC增加，但在疾病进展阶段未检测到。此外，在疾病进展阶段观察到侧脑室中的NPC减少，而在疾病发作和进展阶段检测到海马中的NPC数量没有差异。一些NPC响应于运动神经元变性而分化成神经元样细胞。ALS样转基因小鼠在疾病发作和进展阶段内源性成体NPC的组织和分布为考虑通过增加从头神经发生来再生治疗ALS提供了基础。
Regenerative medicine through neural stem cells (NSCs) or neural progenitor cells (NPCs) has been proposed as an alterative avenue for restoring neurological dysfunction in amyotrophic lateral sclerosis (ALS). It is critical to understand the organization and distribution of endogenous adult NPCs in response to motor neuron degeneration before regenerative medicine can be applied for ALS therapy. For this reason, we analyzed the temporal response of NPCs to motor neuron degeneration in the spinal cord and brain using nestin enhancer-driven LacZ reporter transgenic mice (pNes-Tg mice, control) and bi-transgenic mice containing both the nestin enhancer-driven LacZ reporter gene and mutant G93A-SOD1 gene (Bi-Tg mice). We observed an increase of NPCs in the dorsal horns of the spinal cord at the disease onset and progression stages in the Bi-Tg mice compared with that of age-matched pNes-Tg control mice. In contrast, an increase of NPCs in the ventral horns was detected at the disease progression stage. On the other hand, an increase of NPCs in the motor cortex at the disease-onset stage, but not at the disease progression stage, was detected. Furthermore, a decrease of NPCs in the lateral ventricle at the disease progression stage was observed, whereas no difference in the number of NPCs in the hippocampus was detected at the disease onset and progression stages. Some of the NPCs differentiate into neuron-like cells in response to motor neuron degeneration. The organization and distribution of endogenous adult NPCs in the ALS-like transgenic mice at the disease onset and progression stages provide fundamental bases for consideration of regenerative therapy of ALS by increasing de novo neurogenesis.