Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium‐dependent manner. Issue 10 (14th March 2020)

• Record Type: Journal Article
• Authors: Kim, Jihyun; Adams, Alexandra A.; Gokina, Pradeepa; Zambrano, Brayan; Jayakumaran, Jeyanthan; Dobrowolski, Radek; Maurel, Patrice; Pfister, Bryan J.; Kim, Haesun A.
• Is Part Of: Glia. Volume 68:Issue 10(2020)
• Page Start: 2070
• Page End: 2085
• Publication Date: 2020-03-14
• Subjects: calcium -- Erk1/2 -- MBP -- mechanotransduction -- myelin -- oligodendrocytes -- TBI; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23827
• Languages: English
• ISSNs: 0894-1491

Abstract

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 Ca 2+ and Erk1/2 activation. Chelating Ca 2+ 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 Ca 2+ from the endoplasmic reticulum (ER) and subsequent Ca 2+ ‐dependent activation of Erk1/2. Altogether, our findings characterize an Erk1/2‐dependent mechanotransduction mechanism in mature oligodendrocytes that de‐stabilizes the myelination program. Abstract : Mechanical stretch induces myelin protein loss in mature oligodendrocytes by initiating Ca 2+ ‐dependent Erk1/2 activation. Inhibition of Ca 2+ or Erk1/2 prevents myelin protein loss after stretch injury. The study has implications on myelin loss associated with traumatic brain injury.