| First Author | Yau JL | Year | 2015 |
| Journal | Eur J Neurosci | Volume | 41 |
| Issue | 6 | Pages | 787-92 |
| PubMed ID | 25614240 | Mgi Jnum | J:253314 |
| Mgi Id | MGI:6109417 | Doi | 10.1111/ejn.12836 |
| Citation | Yau JL, et al. (2015) Diurnal and stress-induced intra-hippocampal corticosterone rise attenuated in 11beta-HSD1-deficient mice: a microdialysis study in young and aged mice. Eur J Neurosci 41(6):787-92 |
| abstractText | 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally regenerates active glucocorticoids from their inert forms thereby amplifying intracellular levels within target tissues including the brain. We previously showed greater increases in intra-hippocampal corticosterone (CORT) levels upon Y-maze testing in aged wild-type than in 11beta-HSD1(-/-) mice coinciding with impaired and intact spatial memory, respectively. Here we examined whether ageing influences 11beta-HSD1 regulation of CORT in the dorsal hippocampus under basal conditions during the diurnal cycle and following stress. Intra-hippocampal CORT levels measured by in vivo microdialysis in freely behaving wild-type mice displayed a diurnal variation with peak levels in the evening that were significantly elevated with ageing. In contrast, the diurnal rise in intra-hippocampal CORT levels was greatly diminished in 11beta-HSD1(-/-) mice and there was no rise with ageing; basal intra-hippocampal CORT levels were similar to wild-type controls. Furthermore, a short (3 min) swim stress induced a longer lasting increase in intra-hippocampal CORT levels in wild-type mice than in 11beta-HSD1(-/-) mice despite no genotypic differences in elevation of plasma CORT. These data indicate that 11beta-HSD1 activity contributes substantially to diurnal and stress-induced increases in hippocampal CORT levels. This contribution is even greater with ageing. Thus, 11beta-HSD1 inhibition may be an attractive target for treating cognitive impairments associated with stress or ageing. |
