Browse by author
Lookup NU author(s): Professor Brian Walker
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
© 2015 Elsevier Inc. 11Beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) locally amplifies active glucocorticoids within specific tissues including in brain. In the hippocampus, 11β-HSD1 messenger RNA increases with aging. Here, we report significantly greater increases in intrahippocampal corticosterone (CORT) levels in aged wild-type (WT) mice during the acquisition and retrieval trials in a Y-maze than age-matched 11β-HSD1-/- mice, corresponding to impaired and intact spatial memory, respectively. Acute stress applied to young WT mice led to increases in intrahippocampal CORT levels similar to the effects of aging and impaired retrieval of spatial memory. 11β-HSD1-/- mice resisted the stress-induced memory impairment. Pharmacologic inhibition of 11β-HSD1 abolished increases in intrahippocampal CORT levels during the Y-maze trials and prevented spatial memory impairments in aged WT mice. These data provide the first invivo evidence that dynamic increases in hippocampal 11β-HSD1 regenerated CORT levels during learning and retrieval play a key role in age- and stress-associated impairments of spatial memory.
Author(s): Yau JLW, Wheelan N, Noble J, Walker BR, Webster SP, Kenyon CJ, Ludwig M, Seckl JR
Publication type: Article
Publication status: Published
Journal: Neurobiology of Aging
Print publication date: 01/01/2015
Online publication date: 15/07/2014
Acceptance date: 08/07/2014
ISSN (print): 0197-4580
ISSN (electronic): 1558-1497
Publisher: Elsevier Inc.
PubMed id: 25109766
Altmetrics provided by Altmetric