Amyloid β1-42 oligomer inhibits myelin sheet formation in vitro.
Amyloid β1-42 oligomer inhibits myelin sheet formation in vitro.
复制标题
DOI：
10.1016/j.neurobiolaging.2010.05.007
复制
发表时间：
2012-03
影响因子：
4.2
通讯作者：
Decarli C
中科院分区：
文献类型：
--
作者：
Horiuchi M;Maezawa I;Itoh A;Wakayama K;Jin LW;Itoh T;Decarli C
越来越多的证据表明，白色物质变性有助于神经断开，阿尔茨海默氏病的病理生理基础。虽然这种白色变性部分归因于与神经元变性相关的轴突病变，但淀粉样β（Aβ）蛋白介导的少突胶质细胞损伤可能是另一种机制。为了验证这一假设，我们研究了寡聚体形式的可溶性Aβ对少突胶质细胞谱系细胞存活和分化的影响，使用来自不同发育阶段大鼠的高度纯化的少突胶质细胞培养物。10 μM或更高浓度的Aβ寡聚体降低了成熟少突胶质细胞的存活率，而少突胶质祖细胞（OPC）对Aβ寡聚体介导的细胞毒性具有相对抗性。进一步的研究表明，即使在1 μM的Aβ寡聚体也能促进成熟少突胶质细胞中3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）甲瓒的胞吐，更显著的是，在体外诱导OPCs分化后，抑制髓鞘片的形成。这些结果提示Aβ寡聚体介导的白色变性可能存在一种新的发病机制，这种机制可能损害成年OPCs的髓鞘维持和髓鞘再生，导致髓鞘形成轴突的累积损伤，从而导致神经连接断开。
Accumulating evidence indicates that white matter degeneration contributes to the neural disconnections that underlie Alzheimer’s disease pathophysiology. Although this white matter degeneration is partly attributable to axonopathy associated with neuronal degeneration, amyloid β (Aβ) protein-mediated damage to oligodendrocytes could be another mechanism. To test this hypothesis, we studied effects of soluble Aβ in oligomeric form on survival and differentiation of cells of the oligodendroglial lineage using highly purified oligodendroglial cultures from rats at different developmental stages. Aβ oligomer at 10 μM or higher reduced survival of mature oligodendrocytes, whereas oligodendroglial progenitor cells (OPCs) were relatively resistant to the Aβ oligomer-mediated cytotoxicity. Further study revealed that Aβ oligomer even at 1 μM accelerated 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formazan exocytosis in mature oligodendrocytes, and, more significantly, inhibited myelin sheet formation after induction of in vitro differentiation of OPCs. These results imply a novel pathogenetic mechanism underlying Aβ oligomer-mediated white matter degeneration, which could impair myelin maintenance and remyelination by adult OPCs, resulting in accumulating damage to myelinating axons thereby contributing to neural disconnections.
登录
查看更多内容
影响因子：
14
作者：
Kavcic, Voyko;Ni, Hongyan;Zhu, Tong;Zhong, Jianhui;Duffy, Charles J.
通讯作者：
Duffy, Charles J.
影响因子：
3.3
作者：
de Vries, H;Schrage, C;Hoekstra, D
通讯作者：
Hoekstra, D
影响因子：
4.7
作者：
Chen, SW;Lee, JM;Xu, J
通讯作者：
Xu, J
影响因子：
4.2
作者：
Lintner, RN;Dyer, CA
通讯作者：
Dyer, CA
淀粉样蛋白β肽通过激活中性鞘磷脂酶钙酰胺途径来诱导少突胶质细胞死亡。
影响因子：
7.8
作者：
Lee, Jiunn-Tay;Xu, Jan;Lee, Jin-Moo;Ku, Grace;Han, Xianlin;Yang, Ding-I;Chen, Shawei;Hsu, Chung Y
通讯作者：
Hsu, Chung Y