alexa Memory and learning impairment induced by dexamethasone in senescent but not young mice.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Clinical & Experimental Pharmacology

Author(s): Yao YY, Liu DM, Xu DF, Li WP

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Abstract In this study, the memory and learning impairment induced by dexamethasone in young mice and senescent mice were evaluated by step-down inhibitory avoidance task and passive avoidance test. Colorimetric MTT(tetrazole 3-(4,5-dimethylthiazol-2-yl-)-2,5-diphenyltetrazolium bromide) assay and TUNEL staining were used to investigate the influence of dexamethasone on hippocampal neuronal cell death with amyloid beta-protein. It was determined the effect of dexamethasone on intracellular calcium ([Ca(2+)](i)) with amyloid beta-protein 25-35 by fluorescence imaging with a confocal laser microscope using fluo-3 acetoxymethylester (AM) as a fluorescent dye. The effect of dexamethasone on amyloid beta-protein 25-35-induced nuclear factor kappaB (NF-kappaB) was analyzed by western blot. The results showed that twenty one days dexamethasone exposure resulted in an impairment of memory and learning in senescent but not young mice. Pretreatment of isolated hippocampal neurons with dexamethasone increased the vulnerability of the hippocampal neurons to amyloid beta-protein 25-35, enhanced [Ca(2+)](i) and down-regulated the increased level of nuclear NF-kappaB p65 proteins induced by amyloid beta-protein 25-35. These results demonstrated that glucocorticoids could potentiate the neurotoxic action of amyloid beta-protein by further increasing the level of [Ca(2+)](i) and down-regulating the level of nuclear NF-kappaB protein. Since amyloid beta-protein increases in the brain with aging, glucocorticoids potentiation of the neurotoxic action of amyloid beta-protein maybe one of the mechanisms responsible for glucocorticoids-induced memory and learning impairment in senescent but not young mice, which maybe relevance to the etiology of Alzheimer's disease. This article was published in Eur J Pharmacol and referenced in Journal of Clinical & Experimental Pharmacology

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