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

NEUROBIOLOGY OF AGING

卷:36

Article

Yau, Joyce L. W.^1,2  Wheelan, Nicola^1,2  Noble, June²  Walker, Brian R.²  Webster, Scott P.²  Kenyon, Christopher J.²  Ludwig, Mike³  Seckl, Jonathan R.^1,2 

[1] Univ Edinburgh, Ctr Cognit Aging & Cognit Epidemiol, Edinburgh EH16 4TJ, Midlothian, Scotland

[2] Univ Edinburgh, Queens Med Res Inst, British Heart Fdn Ctr Cardiovasc Sci, Endocrinol Unit, Edinburgh EH16 4TJ, Midlothian, Scotland

[3] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH16 4TJ, Midlothian, Scotland

关键词: Aging;    Stress;    Corticosterone;    Spatial memory;    11 beta-HSD1;    Hippocampus;   

DOI  :  10.1016/j.neurobiolaging.2014.07.007

来源: Elsevier

【 摘 要 】

11Beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) locally amplifies active glucocorticoids within specific tissues including in brain. In the hippocampus, 11 beta-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 11 beta-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. 11 beta-HSD1(-/-) mice resisted the stress-induced memory impairment. Pharmacologic inhibition of 11 beta-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 11 beta-HSD1 regenerated CORT levels during learning and retrieval play a key role in age-and stress-associated impairments of spatial memory. (C) 2015 Elsevier Inc. All rights reserved.

【 授权许可】

Free