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

Authors

Jihyun Kim, Rutgers University-Newark
Alexandra A. Adams, Rutgers University-Newark
Pradeepa Gokina, Rutgers University-Newark
Brayan Zambrano, Rutgers University-Newark
Jeyanthan Jayakumaran, Rutgers University-Newark
Radek Dobrowolski, Rutgers University-Newark
Patrice Maurel, Rutgers University-Newark
Bryan J. Pfister, Newark College of Engineering
Haesun A. Kim, Rutgers University-Newark

Document Type

Article

Publication Date

10-1-2020

Abstract

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.

Identifier

85081723609 (Scopus)

Publication Title

GLIA

External Full Text Location

https://doi.org/10.1002/glia.23827

e-ISSN

10981136

ISSN

08941491

PubMed ID

32170885

First Page

2070

Last Page

2085

Issue

10

Volume

68

Grant

CBIR11PJT012

Fund Ref

National Institutes of Health

Recommended Citation

Kim, Jihyun; Adams, Alexandra A.; Gokina, Pradeepa; Zambrano, Brayan; Jayakumaran, Jeyanthan; Dobrowolski, Radek; Maurel, Patrice; Pfister, Bryan J.; and Kim, Haesun A., "Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium-dependent manner" (2020). Faculty Publications. 4961.
https://digitalcommons.njit.edu/fac_pubs/4961