title: Microglial contribution to oxidative stress in Alzheimer's disease.
abstract: Microglia are the CNS macrophage and are a primary cellular component of plaques in Alzheimer's disease (AD) that may contribute to the oxidative stress associated with chronic neurodegeneration. We now report that superoxide anion production in microglia or macrophages from 3 different species is increased by long term exposure (24 hours) to A beta peptides. Since A beta competes for the uptake of opsonized latex beads and for the production of superoxide anion by opsonized zymosan, a likely site of action are membrane receptors associated with the uptake of opsonized particles or fibers. The neurotoxic fibrillar peptides A beta (1-42) and human amylin increase radical production whereas a non-toxic, non-fibrillar peptide, rat amylin, does not. We also report that the effect of A beta peptides on superoxide anion production is not associated with a concomitant increase in nitric oxide (NO) production in either human monocyte derived macrophages (MDM) or hamster microglia from primary cultures. Since NO is known to protect membrane lipids and scavenge superoxide anion, the lack of A beta-mediated induction of NO production in human microglia and macrophages may be as deleterious as the over-production of superoxide anion induced by chronic exposure to A beta peptides.
authors.affiliation: Department of Physiology, Georgetown University Medical School, Washington, DC 20007, USA. glia01@aol.com
authors.forename: C A
authors.initials: CA
authors.lastname: Colton
authors.forename: O N
authors.initials: ON
authors.lastname: Chernyshev
authors.forename: D L
authors.initials: DL
authors.lastname: Gilbert
authors.forename: M P
authors.initials: MP
authors.lastname: Vitek
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000473:pathology*; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D051381:Rats; D013481:Superoxides / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D013481:Superoxides; D009569:Nitric Oxide