NR AVDG
AU Garcao,P.; Oliveira,C.R.; Agostinho,P.
TI Comparative study of microglia activation induced by amyloid-beta and prion peptides: role in neurodegeneration.
QU Journal of Neuroscience Research 2006 Jul; 84(1): 182-93
PT journal article
AB The inflammatory responses in Alzheimer's disease (AD) and prion-related encephalopathies (PRE) are dominated by microglia activation. Several studies have reported that the amyloid-beta (Abeta) peptides, which are associated with AD, and the pathogenic isoform of prion protein (PrPsc) have a crucial role in neuronal death and gliosis that occur in both of these disorders. In this study, we investigate whether Abeta and PrPsc cause microglia activation per se and whether these amyloidogenic peptides differentially affect these immunoeffector cells. In addition, we also determined whether substances released by Abeta- and PrP-activated microglia induce neuronal death. Cultures of rat brain microglia cells were treated with the synthetic peptides Abeta1-40, Abeta1-42 and PrP106-126 for different time periods. The lipopolysaccharide was used as a positive control of microglia activation. Our results show that Abeta1-40 and PrP106-126 caused similar morphological changes in microglia and increased the production of nitric oxide and hydroperoxides. An increase on inducible nitric oxide synthase expression was also observed in microglia treated with Abeta1-40 or PrP106. However, these peptides affected in a different manner the secretion of interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) secretion. In cocultures of microglia-neurons, it was observed that microglia treated with Abeta1-40 or PrP106-126 induced a comparable extent of neuronal death. The neutralizing antibody for IL-6 significantly reduced the neuronal death induced by Abeta- or PrP-activated microglia. Taken together, the data indicate that Abeta and PrP peptides caused microglia activation and differentially affected cytokine secretion. The IL-6 released by reactive microglia caused neuronal injury.
MH Amyloid beta-Protein/*pharmacology; Analysis of Variance; Animals; Animals, Newborn; Blotting, Western/methods; Cell Survival/drug effects; Cells, Cultured; Coculture Techniques/methods; Comparative Study; Cytokines/metabolism; Gene Expression/*drug effects; Immunohistochemistry/methods; Lipopolysaccharides/pharmacology; Microglia/*drug effects; Neurons/physiology; Nitric Oxide Synthase Type II/metabolism; Nitrites/metabolism; Peptide Fragments/*pharmacology; Prions/*pharmacology; Rats; Rats, Wistar; Reactive Oxygen Species/metabolism; Research Support, Non-U.S. Gov't; Time Factors
AD Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
SP englisch
PO USA