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Publication : Intrahippocampal glucocorticoids generated by 11β-HSD1 affect memory in aged mice.

First Author  Yau JL Year  2015
Journal  Neurobiol Aging Volume  36
Issue  1 Pages  334-43
PubMed ID  25109766 Mgi Jnum  J:218322
Mgi Id  MGI:5617299 Doi  10.1016/j.neurobiolaging.2014.07.007
Citation  Yau JL, et al. (2015) Intrahippocampal glucocorticoids generated by 11beta-HSD1 affect memory in aged mice. Neurobiol Aging 36(1):334-43
abstractText  11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) locally amplifies active glucocorticoids within specific tissues including in brain. In the hippocampus, 11beta-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 11beta-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. 11beta-HSD1(-/-) mice resisted the stress-induced memory impairment. Pharmacologic inhibition of 11beta-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 in vivo evidence that dynamic increases in hippocampal 11beta-HSD1 regenerated CORT levels during learning and retrieval play a key role in age- and stress-associated impairments of spatial memory.
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