Maturation of oligodendrocytes is more sensitive to TNFα than is survival of precursors and immature oligodendrocytes

• Published in: Journal of neuroimmunology Vol. 97; no. 1; pp. 37 - 42
• Main Authors: Cammer, Wendy, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.1999
• Subjects: Animals; Antibodies, Monoclonal; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Lineage - drug effects; Cell Lineage - immunology; Cell Survival - drug effects; Cell Survival - immunology; Cells, Cultured; Development; Glial-cell culture; Myelin basic protein; Myelin Basic Protein - analysis; Myelin Basic Protein - immunology; Oligodendrocyte; Oligodendroglia - chemistry; Oligodendroglia - cytology; Oligodendroglia - immunology; Rats; Rats, Sprague-Dawley; Stem Cells - chemistry; Stem Cells - cytology; Stem Cells - immunology; TNFα; Tumor Necrosis Factor-alpha - pharmacology; Development; TNFα; Glial-cell culture; Oligodendrocyte; Myelin basic protein
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(99)00045-4

TNFα is a cytokine recently found at high levels in multiple sclerosis plaques. The present study addressed the questions whether TNFα might affect oligodendrocytes at various stages of maturation and whether the effects of transient incubation with TNFα would last during subsequent differentiation. Primary glial-cell cultures were treated with 1000 U/ml of TNFα for 48 h, beginning on days 1, 2, 6, 8 and 10 days in vitro, and allowed to grow for up to 3 weeks (total) in vitro. A significant deficit of O4+/MBP+ cells in the TNFα-treated cultures became obvious during the second week. Moreover, the morphology of the O4-positive cells became more complex with time in the control cultures, whereas fewer cells in TNFα-treated cultures developed into cells with sheets of membrane or >four processes. In TNFα-treated cultures, the numbers of O4-positive cells increased by about four-fold during weeks 2 and 3, but the numbers of MBP-positive cells did not and were significantly lower than the numbers of MBP-positive cells in control cultures. The effects of TNFα were apparent 1 to 14 days after treatment, suggesting long-term influences, and could be initiated at diverse stages of maturation. Future testing of hypothetical mechanisms by which TNFα may inhibit oligodendrocyte differentiation should impact on our understanding of the apparent limitations on remyelination in the mature CNS.