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Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner.
Glia ( IF 6.2 ) Pub Date : 2020-03-14 , DOI: 10.1002/glia.23827
Jihyun Kim 1 , Alexandra A Adams 1 , Pradeepa Gokina 1 , Brayan Zambrano 1 , Jeyanthan Jayakumaran 1 , Radek Dobrowolski 1 , Patrice Maurel 1 , Bryan J Pfister 2 , Haesun A Kim 1
Affiliation  

Myelin loss in the brain is a common occurrence in traumatic brain injury (TBI) that results from impact‐induced acceleration forces to the head. Fast and abrupt head motions, either resulting from violent blows and/or jolts, cause rapid stretching of the brain tissue, and the long axons within the white matter tracts are especially vulnerable to such mechanical strain. Recent studies have shown that mechanotransduction plays an important role in regulating oligodendrocyte progenitors cell differentiation into oligodendrocytes. However, little is known about the impact of mechanical strain on mature oligodendrocytes and the stability of their associated myelin sheaths. We used an in vitro cellular stretch device to address these questions, as well as characterize a mechanotransduction mechanism that mediates oligodendrocyte responses. Mechanical stretch caused a transient and reversible myelin protein loss in oligodendrocytes. Cell death was not observed. Myelin protein loss was accompanied by an increase in intracellular Ca2+ and Erk1/2 activation. Chelating Ca2+ or inhibiting Erk1/2 activation was sufficient to block the stretch‐induced loss of myelin protein. Further biochemical analyses revealed that the stretch‐induced myelin protein loss was mediated by the release of Ca2+ from the endoplasmic reticulum (ER) and subsequent Ca2+‐dependent activation of Erk1/2. Altogether, our findings characterize an Erk1/2‐dependent mechanotransduction mechanism in mature oligodendrocytes that de‐stabilizes the myelination program.

中文翻译:

机械拉伸通过以钙依赖性方式激活 Erk1/2 来诱导少突胶质细胞中的髓鞘蛋白丢失。

大脑中的髓鞘丢失是外伤性脑损伤 (TBI) 中常见的情况,这是由撞击引起的头部加速力引起的。快速和突然的头部运动,无论是由猛烈的打击和/或颠簸引起的,都会导致脑组织快速拉伸,而白质束内的长轴突特别容易受到这种机械应变的影响。最近的研究表明,机械转导在调节少突胶质祖细胞向少突胶质细胞分化中起重要作用。然而,关于机械应变对成熟少突胶质细胞的影响及其相关髓鞘的稳定性知之甚少。我们使用体外细胞拉伸装置来解决这些问题,并表征介导少突胶质细胞反应的机械转导机制。机械拉伸导致少突胶质细胞中短暂和可逆的髓鞘蛋白丢失。没有观察到细胞死亡。髓鞘蛋白丢失伴随着细胞内 Ca 的增加2+和 Erk1/2 激活。螯合 Ca 2+或抑制 Erk1/2 激活足以阻止牵张诱导的髓鞘蛋白丢失。进一步的生化分析表明,牵张诱导的髓鞘蛋白丢失是由内质网 (ER)中 Ca 2+的释放和随后的 Erk1/2 的Ca 2+依赖性激活介导的。总之,我们的研究结果表征了成熟少突胶质细胞中 Erk1/2 依赖性机械转导机制,该机制使髓鞘形成程序不稳定。
更新日期:2020-03-14
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