A new model of cuprizone-mediated demyelination/remyelination.
A new model of cuprizone-mediated demyelination/remyelination.
复制标题
DOI：
10.1177/1759091414551955
复制
发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Macklin WB
中科院分区：
文献类型：
--
作者：
Sachs HH;Bercury KK;Popescu DC;Narayanan SP;Macklin WB
在中枢神经系统中，脱髓鞘疾病，如多发性硬化症，会导致毁灭性的长期神经损伤，部分原因是成年人大脑中缺乏有效的髓鞘再生。用于理解调节髓鞘再生的机制的一种模型是铜腙诱导的脱髓鞘，其允许在毒素诱导的脱髓鞘后研究成年动物中的髓鞘再生机制。不幸的是，铜腙模型中脱髓鞘的程度可能会有所不同，这使得理解髓鞘再生过程变得复杂。我们实验室以前的工作表明Akt/mTOR通路调节活跃的髓鞘形成。当给予年轻的出生后小鼠时，mTOR抑制剂雷帕霉素抑制活跃的髓鞘形成。在本研究中，通过在铜腙暴露期间添加雷帕霉素来修改铜腙模型。当一起给药时，cuprizone和雷帕霉素产生更完全的脱髓鞘，并提供了一个更长的时间框架，在此期间，研究髓鞘再生比单独用cuprizone治疗。脱髓鞘的一致性将使我们更好地理解启动髓鞘再生的机制。此外，较慢的髓鞘再生速率提供了更长的时间窗口，以研究调节髓鞘再生的各种因素。这种新的模型cuprizone诱导的脱髓鞘可能有助于识别新的治疗靶点，以提高脱髓鞘疾病的髓鞘再生。
In the central nervous system, demyelinating diseases, such as multiple sclerosis, result in devastating long-term neurologic damage, in part because of the lack of effective remyelination in the adult human brain. One model used to understand the mechanisms regulating remyelination is cuprizone-induced demyelination, which allows investigation of remyelination mechanisms in adult animals following toxin-induced demyelination. Unfortunately, the degree of demyelination in the cuprizone model can vary, which complicates understanding the process of remyelination. Previous work in our laboratory demonstrated that the Akt/mTOR pathway regulates active myelination. When given to young postnatal mice, the mTOR inhibitor, rapamycin, inhibits active myelination. In the current study, the cuprizone model was modified by the addition of rapamycin during cuprizone exposure. When administered together, cuprizone and rapamycin produced more complete demyelination and provided a longer time frame over which to investigate remyelination than treatment with cuprizone alone. The consistency in demyelination will allow a better understanding of the mechanisms initiating remyelination. Furthermore, the slower rate of remyelination provides a longer window of time in which to investigate the diverse contributing factors that regulate remyelination. This new model of cuprizone-induced demyelination could potentially aid in identification of new therapeutic targets to enhance remyelination in demyelinating diseases.
登录
查看更多内容
影响因子：
5.3
作者：
Bercury, Kathryn K.;Dai, JinXiang;Macklin, Wendy B.
通讯作者：
Macklin, Wendy B.
影响因子：
5
作者：
Lindner, M.;Heine, S.;Stangel, M.
通讯作者：
Stangel, M.
影响因子：
2.5
作者：
Lindner, Maren;Fokuhl, Jantje;Stangel, Martin
通讯作者：
Stangel, Martin
影响因子：
4.7
作者：
Hibbits N;Yoshino J;Le TQ;Armstrong RC
通讯作者：
Armstrong RC
影响因子：
16
作者：
Sarbassov, DD;Ali, SM;Sabatini, DM
通讯作者：
Sabatini, DM