Vitamin E increases S100B-mediated microglial activation in an S100B-overexpressing mouse model of pathological aging.
S100B is a calcium-binding protein released by astroglial cells of the brain capable of producing numerous extracellular effects. Although the direct molecular mechanism remains unknown, these effects can be trophic including differentiation, growth, recovery, and survival of neurons when the S100B protein is mainly oxidized and neurotoxic including apoptosis and neuroinflammatory processes marked by microglial activation when in a reduced state. S100B and its receptor RAGE (receptor for advanced glycation end products) have been found to be increased in Alzheimer's disease, Down syndrome, with tissue trauma and ischemia. In the current study, we examined the binding of the S100B receptor (RAGE) on microglial cells and the developmental effects of the antioxidant vitamin E on microglial activation and the upregulation of RAGE in an S100B over-expressing mouse model of pathological aging. We report that RAGE is co-localized on activated microglial cells and vitamin E induced dramatic increases in microglial activation as well as total microglial relative optical density that was accompanied by upregulation of the RAGE receptor, particularly in the CA1 region of the hippocampus. Our findings suggest further investigation into the potential role of vitamin E in reducing the oxidation state of the S100B protein and its influence on neuroinflammatory processes marked by microglial activation in vivo.
Bialowas-McGoey
Lynn A
LA
Department of Psychology, Stony Brook University, Stony Brook, New York, USA. lynn.bialowas@sunysb.edu
Lesicka
Agnieszka
A
Whitaker-Azmitia
Patricia M
PM
D019588:Aging, Premature / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000378:metabolism*; D024505:Tocopherols / Q000494:pharmacology*
D000975:Antioxidants; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; C498977:Mok protein, mouse; D020928:Mitogen-Activated Protein Kinases; D024505:Tocopherols