Alpha-tocopherol (vitamin E) induces rapid, nonsustained proliferation in cultured rat microglia.
Microglial cells undergo cell division in vitro, as well as in vivo after brain injury. Mitotic activity of microglia suggests that they have limited life spans and rely on self-renewal to replace senescent cells. In the current study we examined long-term effects of antioxidants vitamin E and alpha-lipoic acid on cultured rat microglia with respect to proliferative ability, telomere length, telomerase activity, and interleukin-1beta (IL-1beta) production. We report that vitamin E induces dramatic microglial proliferation, as measured by MTT assay and BrdU incorporation, surpassing that of the well-known microglial mitogen granulocyte macrophage-colony stimulating factor, and therefore establishing vitamin E as the most potent, known mitogen for microglia in vitro. The high rate of microglial proliferation resulted in a concomitant decrease in telomere length and telomerase activity. Production of IL-1beta was significantly decreased in vitamin E-treated microglia in vitro. Our findings provide an impetus to investigate potential benefits of vitamin E supplementation on microglial renewal capacity in vivo during aging or after brain injury.
Flanary
Barry E
BE
Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute,Gainesville, 32610-0244, USA.
Streit
Wolfgang J
WJ
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000187:drug effects / Q000502:physiology; D008063:Thioctic Acid / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D024502:alpha-Tocopherol / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000975:Antioxidants; D007375:Interleukin-1; D008934:Mitogens; D008063:Thioctic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019098:Telomerase; D024502:alpha-Tocopherol