Microglial reactivity to beta-amyloid is modulated by astrocytes and proinflammatory factors.
The brains of Alzheimer's disease (AD) patients present activated glial cells, amyloid plaques and dystrophic neurites. The core of amyloid plaques is composed of aggregated amyloid peptide (Abeta), a peptide known to activate glial cells and to have neurotoxic effects. We evaluated the capability of glial cells to mediate Abeta(1-42) cytotoxicity in hippocampal cultures. Conditioned media obtained from microglial cultures exposed to Abeta induced apoptosis of hippocampal cells. This pro-apoptotic effect was not observed in hippocampal cultures exposed to conditioned media obtained from mixed glial (astrocytes and microglia) cultures that had been exposed to Abeta. Microglia exposed to Abeta responded with reactive morphological changes, induction of iNOS, elevated nitric oxide production and decreased reductive metabolism. All these responses were attenuated by the presence of astrocytes. This astrocyte modulation was however, not observed when glial cells were exposed to proinflammatory factors (LPS+Interferon-gamma) alone or in combination with Abeta. Our results suggest that astrocytes and proinflammatory molecules are determining factors in the response of microglia to Abeta.
von Bernhardi
Rommy
R
Department of Neurology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, Chile. rvonb@med.puc.cl
Eugenín
Jaime
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)