| First Author | Sooy K | Year | 2010 |
| Journal | J Neurosci | Volume | 30 |
| Issue | 41 | Pages | 13867-72 |
| PubMed ID | 20943927 | Mgi Jnum | J:165488 |
| Mgi Id | MGI:4837564 | Doi | 10.1523/JNEUROSCI.2783-10.2010 |
| Citation | Sooy K, et al. (2010) Partial deficiency or short-term inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging mice. J Neurosci 30(41):13867-72 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-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 11beta-HSD1 are protected from spatial memory impairments with aging. Here, we tested whether lifelong or short-term decreases in 11beta-HSD1 activity are sufficient to alter cognitive function in aged mice. Aged (24 months old) heterozygous male 11beta-HSD1 knock-out mice, with approximately 60% reduction in hippocampal 11beta-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 11beta-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 11beta-HSD1 inhibitors in the treatment of age-related cognitive impairments. |
