Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer's Disease Model Mouse.
Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer's Disease Model Mouse.
复制标题
氯马斯汀通过预防阿尔茨海默病模型小鼠少突胶质细胞前体细胞的衰老来改善髓鞘质缺陷
DOI：
10.3389/fcell.2021.733945
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Ma QH
中科院分区：
文献类型：
--
作者：
Xie YY;Pan TT;Xu DE;Huang X;Tang Y;Huang W;Chen R;Lu L;Chi H;Ma QH
在阿尔茨海默病（AD）患者和各种小鼠模型的大脑中观察到髓磷脂破坏和髓磷脂修复受损。Clemastine是一种h1 -抗组胺药，通过拮抗M1毒蕈碱受体，显示出在以脱髓鞘为特征的不同神经病理条件下诱导少突胶质前体细胞（OPC）分化和髓鞘形成的能力。在这项研究中，我们研究了老年APPSwe/PS1dE9小鼠（AD模型）是否可以从慢性clemastine治疗中获益。我们发现这种治疗减少了脑淀粉样蛋白沉积，挽救了小鼠的短期记忆缺陷。OPCs、少突胶质细胞和髓磷脂的密度在治疗后增强，而降解的MBP水平降低，这是髓磷脂退化的标志。此外，我们还提出clemastine在阻止OPCs进入细胞衰老状态中的作用，这是最近被证明是AD发病的一个重要原因。因此，clemastine通过防止OPCs衰老在AD中显示出治疗潜力。
Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.
登录
查看更多内容
DOI：
10.1083/jcb.201610113
发表时间：
2017-07-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carroll B;Nelson G;Rabanal-Ruiz Y;Kucheryavenko O;Dunhill-Turner NA;Chesterman CC;Zahari Q;Zhang T;Conduit SE;Mitchell CA;Maddocks ODK;Lovat P;von Zglinicki T;Korolchuk VI
通讯作者：
Korolchuk VI
影响因子：
5.3
作者：
Abiraman, Kavitha;Pol, Suyog U.;Sim, Fraser J.
通讯作者：
Sim, Fraser J.
影响因子：
5.3
作者：
Liu, Jia;Dupree, Jeffrey L.;Casaccia, Patrizia
通讯作者：
Casaccia, Patrizia
影响因子：
14.5
作者：
Cree, Bruce A. C.;Niu, Jianqin;Fancy, Stephen P. J.
通讯作者：
Fancy, Stephen P. J.
影响因子：
3.4
作者：
Jahrling JB;Laberge RM
通讯作者：
Laberge RM