Interleukin-6, beta-amyloid peptide and NMDA interactions in rat cortical neurons.
Neuronal damage in Alzheimer's disease (AD) is thought to involve direct toxicity of beta-amyloid peptide (Abeta) and excitotoxicity involving NMDA receptors (NMDARs) and altered Ca(2+) dynamics. Inflammation agents produced by microglia or astrocytes and associated with senile plaques such as the cytokine interleukin-6 (IL-6) could also contribute. To investigate this possibility, neuronal damage (lactate dehydrogenase assay, LDH, assay) was measured in cultures of rodent cortical neurons chronically treated with IL-6, Abeta or Abeta plus IL-6 and acutely treated with NMDA. Both Abeta and NMDA produced neuronal damage and this effect was larger with combined treatment. IL-6 did not produce significant neuronal damage but the largest neuronal damage was observed in cultures exposed to all three factors. IL-6 and Abeta enhanced Ca(2+) responses to NMDA and combined treatment produced the largest effect. These results are consistent with a role for interactions between Abeta, NMDA and IL-6 in the neuronal loss in AD.
Qiu
Zhihua
Z
Department of Neuropharmacology, CVN11, The Scripps Research Institute, 10666 N. Torrey Pine Road, La Jolla, CA 92037, USA.
Gruol
Donna L
DL
D000544:Alzheimer Disease / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004347:Drug Interactions / Q000276:immunology; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005333:Fetus; D018698:Glutamic Acid / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000276:immunology / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018690:Excitatory Amino Acid Agonists; D015850:Interleukin-6; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate