Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus
Section snippets
Animal surgery and tissue preparation
Kainate (Sigma, St Louis, MO, U.S.A.) was administered to adult female Sprague–Dawley rats (200–250 g, Korea Institute of Science and Technology, Seoul, Korea; 10 mg/kg, i.p.) and adult female golden hamsters (100–150 g, Harlan Sprague Dawley, IN, U.S.A.; 15 mg/kg, i.p.). At these doses, all of the animals showed seizure activity within 1 h that often persisted for 3–4 h. The animals were killed at 30 min, 4, 8, 24 and 72 h after kainate treatment. In experiments to investigate the effect of MK-801,
Kainate-induced neurodegeneration in the rat and the hamster
We first examined the degeneration pattern of hippocampal neurons in the hamster after the systemic administration of kainate. Compared with the rat, seizure behavior and neuronal death in the hamster were reproducibly observed following administration of kainate (15 mg/kg, i.p.). Kainate-induced mortality was less than 5% in the hamster, suggesting that it is appropriate for the study of kainate neurotoxicity in vivo. The hilar neurons in the rat and the hamster were severely damaged within 4 h
Discussion
Systemic injections of kainate produce widespread neuronal death, primarily in the CA3 area of rat and in the CA1 area of the hamster, while they cause degeneration of hilar neurons in both animals. The activation of NF-κB is observed selectively in degenerating neurons of the hippocampal formation. The kainate-induced NF-κB activation and neurodegeneration of CA1 neurons, but not those in the other hippocampal subfields, in the hamster appear to depend upon the activation of NMDA receptors.
The
Acknowledgements
This study was supported by the academic research fund of the Ministry of Education, Republic of Korea, BSRI-97-4418 (B.J.G.).
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S. J. Won and H. W. Ko contributed equally to this paper.