title: Alpha-tocopherol (vitamin E) induces rapid, nonsustained proliferation in cultured rat microglia.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute,Gainesville, 32610-0244, USA.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Flanary
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Streit
mesh_terms: 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
chemical_list: D000975:Antioxidants; D007375:Interleukin-1; D008934:Mitogens; D008063:Thioctic Acid; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019098:Telomerase; D024502:alpha-Tocopherol