Kainate exacerbates beta-amyloid toxicity in rat hippocampus.
We have previously shown that beta-amyloid (Abeta) increased the excitotoxicity of ibotenate, an N-methyl-D-aspartate (NMDA) receptor agonist, to hippocampal neurons of rats. In this report, non-toxic amounts of kainate were co-injected with Abeta into rat hippocampus. Nissl-stained brain sections revealed that Abeta/kainate co-injection exerted synergistic neuronal degeneration in the hippocampus as well as that by Abeta/ibotenate co-injection. MK-801, an NMDA receptor antagonist, blocked the neuronal loss induced by Abeta/ibotenate co-injection, but not by Abeta/kainate co-injection. On the other hand, 6-cyano-7-nitroquinoxaline-2, 3-dione, a kainate receptor antagonist, suppressed the neuronal loss induced by the Abeta/kainate co-injection, but not that by the Abeta/ibotenate co-injection. This suggests that Abeta increases the sensitivity of both the NMDA receptor and the kainate receptor.
Morimoto
Kiyoshi
K
Neuroscience and Immunology Research Laboratories, Sankyo Co, Ltd, 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. morimo@shina.sankyo.co.jp
Oda
Tomiichiro
T
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D007608:Kainic Acid