Elsevier

Neuroscience

Volume 94, Issue 1, September 1999, Pages 83-91
Neuroscience

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

https://doi.org/10.1016/S0306-4522(99)00196-7Get rights and content

Abstract

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.

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.

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