Hypoxia alters cell cycle regulatory protein expression and induces premature maturation of oligodendrocyte precursor cells.
BACKGROUND
Periventricular white matter injury (PWMI) is a common form of brain injury sustained by preterm infants. A major factor that predisposes to PWMI is hypoxia. Because oligodendrocytes (OLs) are responsible for myelination of axons, abnormal OL development or function may affect brain myelination. At present our understanding of the influences of hypoxia on OL development is limited. To examine isolated effects of hypoxia on OLs, we examined the influences of hypoxia on OL development in vitro.


RESULTS
Cultures of oligodendrocyte precursor cells (OPCs) were prepared from mixed glial cultures and were 99% pure. OPCs were maintained at 21% O(2) or hypoxia (1% or 4% O(2)) for up to 7 days. We observed that 1% O(2) lead to an increase in the proportion of myelin basic protein (MBP)-positive OLs after 1 week in culture, and a decrease in the proportion of platelet-derived growth factor receptor alpha (PDGFRalpha)-positive cells suggesting premature OL maturation. Increased expression of the cell cycle regulatory proteins p27(Kip1) and phospho-cdc2, which play a role in OL differentiation, was seen as well.


CONCLUSIONS
These results show that hypoxia interferes with the normal process of OL differentiation by inducing premature OPC maturation.
Akundi
Ravi Shankar
RS
Yale Child Health Research Center, Section of Developmental Biology & Endocrinology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Rivkees
Scott A
SA
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001973:Bromodeoxyuridine; D016203:CDC2 Protein Kinase; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases; D000860:Hypoxia / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats
D019926:Cyclin B; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine