| Title | Partial deficiency or short-term inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging mice. |
| Publication Type | Journal Article |
| Year of Publication | 2010 |
| Authors | Sooy K, Webster SP, Noble J, Binnie M, Walker BR, Seckl JR, Yau JL |
| Journal | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| Volume | 30 |
| Issue | 41 |
| Pagination | 13867-72 |
| Date Published | 2010 Oct 13 |
| ISSN | 1529-2401 |
| Keywords | 11-beta-Hydroxysteroid Dehydrogenase Type 1, Aging, Analysis of Variance, Animals, Cognition, Corticosterone, Hippocampus, Male, Maze Learning, Mice, Mice, Knockout, Radioimmunoassay, Time Factors |
| Abstract | 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids (GCs) from intrinsically inert 11-keto substrates inside cells, including neurons, thus amplifying steroid action. Excess GC action exerts deleterious effects on the hippocampus and causes impaired spatial memory, a key feature of age-related cognitive dysfunction. Mice with complete deficiency of 11β-HSD1 are protected from spatial memory impairments with aging. Here, we tested whether lifelong or short-term decreases in 11β-HSD1 activity are sufficient to alter cognitive function in aged mice. Aged (24 months old) heterozygous male 11β-HSD1 knock-out mice, with ∼60% reduction in hippocampal 11β-reductase activity throughout life, were protected against spatial memory impairments in the Y-maze compared to age-matched congenic C57BL/6J controls. Pharmacological treatment of aged C57BL/6J mice with a selective 11β-HSD1 inhibitor (UE1961) for 10 d improved spatial memory performance in the Y-maze (59% greater time in novel arm than vehicle control). These data support the use of selective 11β-HSD1 inhibitors in the treatment of age-related cognitive impairments. |
| Alternate Journal | J. Neurosci. |
