Intrahippocampal glucocorticoids generated by 11β-HSD1 affect memory in aged mice
Open accessAbstract
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 in vivo 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.
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Aging-associated memory impairments were prevented in 11β-HSD1-knockout animals.
“Indeed, the enzyme, 11β-hydroxysteroid dehydrogenase (11β-HSD1), involved in the conversion of the inactive corticosterone into its active form, was increased with aging (Barrientos et al, 2015), and aging-associated memory impairments were prevented in 11β-HSD1-knockout animals (Yau et al, 2015).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Yau et al, 2015
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- Quervain D.J.F. Roozendaal B. McGaugh J.L. Stress and glucocorticoids impair retrieval of long-term spatial memory Nature 394 1998 787 790 9723618
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Microglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · see citing works
- Authors
- Yau, J. L. W., Wheelan, N., Noble, J., Walker, B. R., Webster, S. P., Kenyon, C. J., Ludwig, M., & Seckl, J. R.
- Affiliations
- British Heart Foundation Centre for Cardiovascular Science (GB)
- University of Edinburgh (GB)
- Corresponding author
- Yau, Joyce L.W.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 36
- Issue
- 1
- Pages
- 334-343
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC4706164
- OpenAlex
- W2014873425
- Cited by
- 45
- References
- 48
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 6 · 2020: 6 · 2019: 6 · 2018: 2 · 2017: 6 · 2016: 3 · 2015: 5 · 2014: 1
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, other-oa)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- MRC (G0501596)
- CCACE
- Biotechnology and Biological Sciences Research Council
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- 11β-hydroxysteroid dehydrogenase type 1, glucocorticoids, corticosterone, hippocampus, aging, spatial memory, memory retrieval, acute stress, stress-induced memory impairment, Y-maze
- MeSH terms
- Aging, Animals, Glucocorticoids, Hippocampus, Male, Memory Disorders, Mice, Inbred C57BL, Pyrazoles, RNA, Messenger, Stress, Psychological, Thiophenes, Maze Learning, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Molecular Targeted Therapy, Spatial Memory
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