Fleeting activation of ionotropic glutamate receptors sensitizes cortical neurons to complement attack.

Journal Article (Journal Article)

Insidious attack of cortical neurons by complement has been implicated in Alzheimer's and other neurodegenerative diseases. Excitotoxicity, triggered by excessive activation of glutamate receptors, has been implicated in neuronal death following diverse insults, including ischemia and seizures. Clinical studies suggested that a minimal excitotoxic insult might sensitize neurons to complement attack. We found that fleeting activation of ionotropic glutamate receptors sensitizes neurons but not astrocytes to complement attack. The complement molecule effecting cytotoxicity was the membrane attack complex. The site within the complement cascade at which sensitization was effected was the membrane attack pathway. Sensitization mediated by glutamate receptor activation required Ca(2+)(o) and generation of reactive oxygen species. These in vitro findings predict that a fleeting excitotoxic insult could act synergistically with complement to destroy cortical neurons and accelerate neurological deterioration.

Full Text

Duke Authors

Cited Authors

  • Xiong, ZQ; McNamara, JO

Published Date

  • October 24, 2002

Published In

Volume / Issue

  • 36 / 3

Start / End Page

  • 363 - 374

PubMed ID

  • 12408841

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/s0896-6273(02)00977-7


  • eng

Conference Location

  • United States