Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner.

Jihyun Kim, Alexandra A Adams, Pradeepa Gokina, Brayan Zambrano, Jeyanthan Jayakumaran, Radek Dobrowolski, Patrice Maurel, Bryan J Pfister, Haesun A Kim

Glia 2020 Oct

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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. © 2020 Wiley Periodicals, Inc.

Citation

Jihyun Kim, Alexandra A Adams, Pradeepa Gokina, Brayan Zambrano, Jeyanthan Jayakumaran, Radek Dobrowolski, Patrice Maurel, Bryan J Pfister, Haesun A Kim. Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner. Glia. 2020 Oct;68(10):2070-2085