Oxidative stress disrupts oligodendrocyte maturation.
Periventricular white matter injury (PWMI) is the leading cause of chronic neurologic injury among survivors of preterm birth. The hallmark of PWMI is hypomyelination and a lack of mature, myelinating oligodendrocytes. Oligodendrocytes undergo a well-characterized lineage progression from neural stem cell to mature oligodendrocyte. Oligodendrocyte precursors have increased susceptibility to oxidative and free radical-mediated injury compared with mature oligodendrocytes as a result of lower levels of antioxidant enzymes and free radical scavengers. In this study, we show that oxidative stress disrupts oligodendrocyte differentiation by two mechanisms. First, oxidizing agents decrease the expression of key genes that promote oligodendrocyte differentiation from neural stem cells and increase the expression of genes known to inhibit differentiation. Second, global histone acetylation persists under conditions of oxidative stress, further contributing to the prevention of oligodendrocyte differentiation. Both of these mechanisms result in the arrest of oligodendrocyte differentiation without an increase in cell death.
French
Heather Morein
HM
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
Reid
Mary
M
Mamontov
Polina
P
Simmons
Rebecca A
RA
Grinspan
Judith B
JB
D000107:Acetylation; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009836:Oligodendroglia / Q000166:cytology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D006657:Histones