Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Administration of the excitotoxin kainate produces seizure activity and sel ective neuronal death in various brain areas. We examined the degeneration pattern of hippocampal neurons following systemic injections of kainate in the hamster and the rat. As reported, treatment with kainate resulted in se vere neuronal loss in the hilus and CA3 in the rat. While the hilar neurons were also highly vulnerable to kainate in the hamster, neurons in the CAI area, but not CA3, were highly sensitive to kainate. In both animals, immun oreactivity to anti-p50 nuclear factor kappa B antibody was increased in nu clei of the hilar neurons within 4 h following administration of kainate. K ainate treatment also increased the nuclear factor kappa B immunoreactivity in hamster CA1 neurons and rat CA3 neurons 24 h later. Neurons showing int ense nuclear factor kappa B signal were stained with acid fuchsin. Kainate also increased DNA binding activity of p50 and p65 nuclear factor kappa B i n the nuclear extract of the hippocampal formation as analysed by electroph oretic mobility shift assay in the hamster, suggesting that activation of n uclear factor kappa B may contribute to kainate-induced hippocampal degener ation. Administration of 100 nmol dizocilpine maleate 3 h prior to kainate attenuated kainate-induced activation of nuclear factor kappa B and neurona l death in CA1 in the hamster. The present study provides evidence that the differential vulnerability of neurons in the rat and the hamster hippocampus to kainate is partly mediate d by mechanisms involving N-methyl-D-aspartate-dependent activation of nucl ear factor kappa B. (C) 1999 IBRO. Published by Elsevier Science Ltd.