Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Yau, J.L. et al.

Yau, Noble, Kenyon, Hibberd, Kotelevtsev, Mullins, Seckl,

Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments.

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) intracellularly regenerates active corticosterone from circulating inert 11-dehydrocorticosterone (11-DHC) in specific tissues. The hippocampus is a brain structure particularly vulnerable to glucocorticoid neurotoxicity with aging. In intact hippocampal cells in culture, 11beta-HSD-1 acts as a functional 11beta-reductase reactivating inert 11-DHC to corticosterone, thereby potentiating kainate neurotoxicity. We examined the functional significance of 11beta-HSD-1 in the central nervous system by using knockout mice. Aged wild-type mice developed elevated plasma corticosterone levels that correlated with learning deficits in the watermaze. In contrast, despite elevated plasma corticosterone levels throughout life, this glucocorticoid-associated learning deficit was ameliorated in aged 11beta-HSD-1 knockout mice, implicating lower intraneuronal corticosterone levels through lack of 11-DHC reactivation. Indeed, aged knockout mice showed significantly lower hippocampal tissue corticosterone levels than wild-type controls. These findings demonstrate that tissue corticosterone levels do not merely reflect plasma levels and appear to play a more important role in hippocampal functions than circulating blood levels. The data emphasize the crucial importance of local enzymes in determining intracellular glucocorticoid activity. Selective 11beta-HSD-1 inhibitors may protect against hippocampal function decline with age.[1]

References

Lack of tissue glucocorticoid reactivation in 11beta -hydroxysteroid dehydrogenase type 1 knockout mice ameliorates age-related learning impairments. Yau, J.L., Noble, J., Kenyon, C.J., Hibberd, C., Kotelevtsev, Y., Mullins, J.J., Seckl, J.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.