Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus.
Administration of the excitotoxin kainate produces seizure activity and selective 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 severe 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 CA1 area, but not CA3, were highly sensitive to kainate. In both animals, immunoreactivity to anti-p50 nuclear factor kappa B antibody was increased in nuclei of the hilar neurons within 4 h following administration of kainate. Kainate treatment also increased the nuclear factor kappa B immunoreactivity in hamster CA1 neurons and rat CA3 neurons 24 h later. Neurons showing intense nuclear factor kappa B signal were stained with acid fuchsin. Kainate also increased DNA binding activity of p50 and p65 nuclear factor kappa B in the nuclear extract of the hippocampal formation as analysed by electrophoretic mobility shift assay in the hamster, suggesting that activation of nuclear factor kappa B may contribute to kainate-induced hippocampal degeneration. Administration of 100 nmol dizocilpine maleate 3 h prior to kainate attenuated kainate-induced activation of nuclear factor kappa B and neuronal 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 mediated by mechanisms involving N-methyl-D-aspartate-dependent activation of nuclear factor kappa B.
Won
S J
SJ
Department of Pharmacology, Ajou University School of Medicine, Suwon, Kyungkido, South Korea.
Ko
H W
HW
Kim
E Y
EY
Park
E C
EC
Huh
K
K
Jung
N P
NP
Choi
I
I
Oh
Y K
YK
Shin
H C
HC
Gwag
B J
BJ
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D006224:Cricetinae; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D008647:Mesocricetus; D016202:N-Methylaspartate / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016328:NF-kappa B; D009498:Neurotoxins; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007608:Kainic Acid