Apoptosis of oligodendrocytes in secondary cultures from neonatal rat brains.
The plaques in multiple sclerosis (MS) autopsy tissue contain tumor necrosis factor-alpha (TNF-alpha) at high concentrations. Moreover, microglia are able to convert L-tryptophan to quinolinic acid. Thus, TNF-alpha and quinolinic acid are endogenous compounds which may compromise oligodendrocytes during inflammatory demyelination. It is also known that cellular functions depend on adequate concentrations of glutathione (GSH). As some apoptotic oligodendrocytes have been observed in MS plaques, it was therefore logical to determine whether oligodendrocyte apoptosis would occur in response to TNF-alpha, quinolinic acid or GSH depletion. Oligodendrocytes were treated in vitro with TNF-alpha, quinolinic acid and the GSH-depleting agent, buthionine sulfoximine (BSO), respectively, and the numbers of intact and apoptotic cells were counted. TNF-alpha reduced the numbers of mature oligodendrocytes, but not immature oligodendrocytes, without producing apoptosis. Quinolinic acid and BSO each caused oligodendrocyte loss via apoptosis, and GSH ethyl ester partly protected the cells against BSO. The data suggest that oligodendrocytes undergo apoptosis under adverse conditions that result from an endogenous toxicant or depletion of GSH.
Cammer
Wendy
W
Department of Neurology, F-140, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. wcammer@aecom.yu.edu
D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000166:cytology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002478:Cells, Cultured; D009836:Oligodendroglia / Q000166:cytology* / Q000187:drug effects; D017378:Quinolinic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000963:Antimetabolites; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D019328:Buthionine Sulfoximine; D017378:Quinolinic Acid