Abstract
1. The amnesia induced by various stress stimuli through hypoxia and cerebral ischemia was evaluated by the shortening of the response latency in a step-through task in mice.
2. The hypoxia-induced amnesia was reduced by cromakalim, a K+ channel opener (KCO), given 10 min before or immediately after the hypoxic treatment.
3. Similarly, the ischemia-induced amnesia was also reduced by cromakalim given 30min before the occlusion.
4. In ischemic-induced amnesic mice, pyknotic cells, indicating the condensation of chromatin, were observed histochemically at the dentate gyrus granule cells in hippocampal regions 96 hr after ischemic treatment. In addition, cromakalim inhibited the induction of pyknotic cells.
5. These results suggest that KCOs might produce prophylactically neuroprotective effects against hypoxia- and cerebral ischemia-induced amnesia.
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REFERENCES
Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., and Nicotera, P. (1995). Glutamate-induced neuronal death: A succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15:961–973.
Carpenter, G. A., and Grossberg, S. (1993). Normal and amnesic learning, recognition and memory by neural model of cortico-hippocampal interactions. Trends Neurosci. 16:131–137.
Edward, G., and Weston, A. H. (1993). The pharmacology of ATP-sensitive potassium channel. Annu. Rev. Pharmacol. Toxicol. 33:597–693.
Escande, D., and Cavero, I. (1992). K+ channel openers and “natural” cardioprotection. Trends Pharmacol. Sci. 13:269–272.
Finta, E. P., Harms, L., Sevcik, J., Fischer, H.-D., and Illes, P. (1993). Effects of potassium channel openers and their antagonists on rat locus coeruleus neurons. Br. J. Pharmacol. 109:308–315.
Grover, G. J., McCullough, J. R., D'Alonzo, A. J., Sargent, C. A., and Atwal, K. S. (1995). Cardioprotective profile of the cardiac-selective ATP-sensitive potassium channel opener BMS-180448. J. Cardiovasc. Pharmacol. 25:40–50.
Hahn, J. S., Aizenman, E., and Lipton, S. A. (1988). Central Mammalian neurons resistant to glutamate toxicity and made sensitive by elevated extracellular calcium: Toxicity blocked by the N-methyl-D-aspartate antagonist MK-801. Proc. Natl. Acad. Sci. USA 85:6556–6560.
Haley, T. J., and McCormick, W. G. (1957). Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. Br. J. Pharmacol. 12:12–15.
Hamilton, T. C., Weir, S. W., and Weston, A. H. (1986). Comparison of the effects of BRL 34915 and verapamil on electrical and mechanical activity in rat portal vein. Br. J. Pharmacol. 88:103–111.
Heurteaux, C., Bertaina, V., Widmann, C., and Lazdunski, M. (1993). K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, amyloid β-protein precursor genes and neuronal death in rat hippocampus. Proc. Natl. Acad. Sci. USA 90:9431–9435.
Heurteaux, C., Lauritzen, I., Widmann, C., and Lazdunski, M. (1995). Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc. Natl. Acad. Sci. USA 92:4666–4670.
Jodar, L., Takahashi, M., and Kaneto, H. (1996). FS stress induced long-lasting memory facilitation: Involvement of cholinergic pathways. Pharmacol. Biochem. Behav. 53: 735–740.
Kojima, M., and Kaneto, H. (1989). Preparation of cerebral ischemia-induced amnesic model in mice and ameliorative effect of several compounds on the model. Folia Pharmacol. Japon. 94:223–228.
Mourre, C., Ben-Ari, Y., Bernardi, H., Fosset, M., and Lazdunski, M. (1989). Antidiabetic sulfonylureas: Localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices. Brain Res. 486:159–164.
Mourre, C., Widmann, C., and Lazdunski, M. (1991). Specific hippocampal lesions indicate the presence of sulfonylurea binding sites associated to ATP-sensitive K+ channels both post-synaptically and on mossy fibers. Brain Res. 540:340–344.
Phillis, J. W., and O'Regan, M. H. (1996). Mechanisms of glutamate and aspartate release in the ischemic rat cerebral cortex. Brain Res. 730:150–164.
Quast, U., and Cook, N. S. (1989). Moving together: K+ channel openers and ATP-sensitive K+ channels. Trends Pharmacol. Sci. 10:431–435.
Szatkowski, M., and Attwell, D. (1994). Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends Neurosci. 17:359–365.
Yung, R. S. K. During, M. J., Aquila, W. J., Tendler, D., and Ley, E. (1992). Hypoxia increases extracellular concentrations of excitatory and inhibitory neurotransmitters in subsequently induced seizure: In vivo microdialysis study in the rabbit. Exp. Neurol. 117:204–209.
Zini, S., Roisin, M. P., Armengaud, C., and Ben-Ari, Y. (1993). Effect of potassium channel modulators on the release of glutamate induced by ischaemic-like conditions in rat hippocampal slices. Neurosci. Lett. 153:202–205.
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Nakao, K., Tokuyama, S., Takahashi, M. et al. Antiamnesic Action of Cromakalim, A Potassium Channel Opener, in Mice Treated with Hypoxia- and Cerebral Ischemia-Type Stress Stimuli. Cell Mol Neurobiol 18, 429–436 (1998). https://doi.org/10.1023/A:1022553616572
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DOI: https://doi.org/10.1023/A:1022553616572