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• W2553501166 abstract "Mice lacking the intracellular glucocorticoid‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐ HSD 1) are protected from age‐related spatial memory deficits. 11β‐ HSD 1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β‐ HSD 1 may underlie the improved memory in aged 11β‐ HSD 1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β‐ HSD 1 deficient mice. In the present study, transgenic mice with forebrain‐specific overexpression of 11β‐ HSD 1 (Tg) were intercrossed with global 11β‐ HSD 1 knockout mice ( HSD 1 KO ) to examine the influence of forebrain and peripheral 11β‐ HSD 1 activity on spatial memory in aged mice. Transgene‐mediated delivery of 11β‐ HSD 1 to the hippocampus and cortex of aged HSD 1 KO mice reversed the improved spatial memory retention in the Y‐maze but not spatial learning in the watermaze. Brain‐derived neurotrophic factor ( BDNF ) mRNA levels in the hippocampus of aged HSD 1 KO mice were increased compared to aged wild‐type mice. Rescue of forebrain 11β‐ HSD 1 reduced BDNF mRNA in aged HSD 1 KO mice to levels comparable to aged wild‐type mice. These findings indicate that 11β‐ HSD 1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild‐type mice, although 11β‐ HSD 1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice." @default.
• W2553501166 created "2016-11-30" @default.
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• W2553501166 date "2017-01-01" @default.
• W2553501166 modified "2023-10-18" @default.
• W2553501166 title "Forebrain-Specific Transgene Rescue of 11β-HSD1 Associates with Impaired Spatial Memory and Reduced Hippocampal Brain-Derived Neurotrophic Factor mRNA Levels in Aged 11β-HSD1 Deficient Mice" @default.
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• W2553501166 doi "https://doi.org/10.1111/jne.12447" @default.
• W2553501166 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5244685" @default.
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• W2553501166 hasPublicationYear "2017" @default.
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