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Oxidative stress disrupts oligodendrocyte maturation
Author(s) -
French Heather Morein,
Reid Mary,
Mamontov Polina,
Simmons Rebecca A.,
Grinspan Judith B.
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22139
Subject(s) - oligodendrocyte , oxidative stress , microbiology and biotechnology , neural stem cell , biology , stem cell , neuroscience , myelin , biochemistry , central nervous system
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. © 2009 Wiley‐Liss, Inc.