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

✍ Scribed by Yi Pang; Zhengwei Cai; Philip G. Rhodes

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 432 KB
• Volume: 80
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20450

✦ Synopsis

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 þ OL progenitors as well as the O4 þ prooligodendrocytes (pro-OLs) were more susceptible to tumor necrosis factor-a (TNF-a) cytotoxicity than the O4 þ /O1 þ 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-a treatment. Cell death, presumably by apoptosis as evidenced by TUNEL staining and caspase-3 activation, was observed following TNF-a treatment. Corresponding to TNF-ainduced apoptosis, cell survival rate decreased in a time-and dose-dependent manner. The sensitivity of different OL developmental stages to TNF-a decreased with the progression of cell maturation. However, this differential response was not related to differentially expressed TNF-a receptors. Consistent with reports that progenitor cells are preferentially injured in PVL, our results may further support the role of TNF-a as a potential mediator of PVL.