Effect of tumor necrosis factor-α on developing optic nerve oligodendrocytes in culture

There is increasing evidence that proinflammatory cytokines are involved in the development of periventricular leukomalacia (PVL), a condition in which developing oliodendrocytes (OLs) are preferentially injured. In the present study, we utilized an in vitro assay to demonstrate that the A2B5+ OL pr...

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Bibliographic Details
Published in:Journal of neuroscience research 2005-04, Vol.80 (2), p.226-234
Main Authors: Pang, Yi, Cai, Zhengwei, Rhodes, Philip G.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
apoptosis
Cell Survival - physiology
Cells, Cultured
development
Oligodendroglia - cytology
Oligodendroglia - physiology
Optic Nerve - cytology
Optic Nerve - growth & development
Optic Nerve - physiology
proliferation
Rats
Tumor Necrosis Factor-alpha - pharmacology
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Summary:There is increasing evidence that proinflammatory cytokines are involved in the development of periventricular leukomalacia (PVL), a condition in which developing oliodendrocytes (OLs) are preferentially injured. In the present study, we utilized an in vitro assay to demonstrate that the A2B5+ OL progenitors as well as the O4+ prooligodendrocytes (pro‐OLs) were more susceptible to tumor necrosis factor‐α (TNF‐α) cytotoxicity than the O4+/O1+ immature OLs. OL progenitors were isolated from optic nerves of 7‐day‐old rat pups and cultured in chemically defined medium supplemented with platelet‐derived growth factor and basic fibroblast growth factor. OL progenitors were allowed to differentiate into pro‐OLs and immature OLs under special cultural conditions. Cells at three different developmental stages were subjected to TNF‐α treatment. Cell death, presumably by apoptosis as evidenced by TUNEL staining and caspase‐3 activation, was observed following TNF‐α treatment. Corresponding to TNF‐α‐induced apoptosis, cell survival rate decreased in a time‐ and dose‐dependent manner. The sensitivity of different OL developmental stages to TNF‐α decreased with the progression of cell maturation. However, this differential response was not related to differentially expressed TNF‐α receptors. Consistent with reports that progenitor cells are preferentially injured in PVL, our results may further support the role of TNF‐α as a potential mediator of PVL. © 2005 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.20450