Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis.
Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis.
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DOI：
10.1038/nn.3357
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发表时间：
2013-05
影响因子：
25
通讯作者：
Bergles, Dwight E.
中科院分区：
文献类型：
--
作者：
Kang, Shin H.;Li, Ying;Fukaya, Masahiro;Lorenzini, Ileana;Cleveland, Don W.;Ostrow, Lyle W.;Rothstein, Jeffrey D.;Bergles, Dwight E.
少突胶质细胞与轴突结合以建立髓鞘并为神经元提供代谢支持。在ALS小鼠的脊髓中，少突胶质细胞下调将糖酵解底物转移到神经元的转运蛋白，并且少突胶质细胞祖细胞（NG2+细胞）表现出增强的增殖和分化，尽管少突胶质细胞中这些变化的原因尚不清楚。在这里，我们报告说，有广泛的变性灰质少突胶质细胞在脊髓ALS小鼠发病前的疾病。虽然形成了新的少突胶质细胞，但它们未能成熟，导致进行性脱髓鞘。少突胶质细胞功能障碍在人类ALS中也很普遍，因为在ALS患者的运动皮质和脊髓中观察到灰质脱髓鞘和NG2+细胞的反应性变化。从少突胶质细胞中选择性去除突变SOD 1显著延迟了ALS小鼠的疾病发作并延长了存活时间，这表明ALS相关基因通过直接损害少突胶质细胞的功能增强了运动神经元的脆弱性并加速了疾病。
Oligodendrocytes associate with axons to establish myelin and provide metabolic support to neurons. In the spinal cord of ALS mice, oligodendrocytes downregulate transporters that transfer glycolytic substrates to neurons and oligodendrocyte progenitors (NG2+ cells) exhibit enhanced proliferation and differentiation, although the cause of these changes in oligodendroglia is unknown. Here we report that there is extensive degeneration of gray matter oligodendrocytes in the spinal cord of ALS mice before disease onset. Although new oligodendrocytes were formed, they failed to mature, resulting in progressive demyelination. Oligodendrocyte dysfunction also is prevalent in human ALS, as gray matter demyelination and reactive changes in NG2+ cells were observed in motor cortex and spinal cord of ALS patients. Selective removal of mutant SOD1 from oligodendroglia substantially delayed disease onset and prolonged survival in ALS mice, suggesting that ALS-linked genes enhance the vulnerability of motor neurons and accelerate disease by directly impairing the function of oligodendrocytes.
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影响因子：
5.3
作者：
Higuchi, M;Zhang, B;Lee, VMY
通讯作者：
Lee, VMY
影响因子：
4.2
作者：
Buntinx, M;Moreels, M;Ameloot, M
通讯作者：
Ameloot, M
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
5.3
作者：
Gong, YH;Parsadanian, AS;Elliott, JL
通讯作者：
Elliott, JL
影响因子：
1.5
作者：
Doerflinger, NH;Macklin, WB;Popko, B
通讯作者：
Popko, B