ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Partial deficiency or short-term inhibition of 11beta-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 79 citations in OpenAlex.
- Plasma pTau181 Predicts Clinical Progression in a Phase 2 Randomized Controlled Trial of the 11β-HSD1 Inhibitor Xanamem® for Mild Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Trial
- Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™).British journal of pharmacology · 2017Trial
- Why 11β-HSD1 inhibitors show variable efficacy in Alzheimer's therapy: an APOE4-dependent HSD11B1 mechanism.Theranostics · 2026Article
- Improvement in Insulin Sensitivity Prevents Decline in Glucose Uptake, Functional Connectivity, and Volume in the Insulin Resistant Human Brain.Research square · 2025Article
- Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.Clinical pharmacology in drug development · 2025Review
- An Interaction between Brain-Derived Neurotrophic Factor and Stress-Related Glucocorticoids in the Pathophysiology of Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Brain 11β-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer's Disease and Cognitively Normal Individuals.Journal of Alzheimer's disease : JAD · 2024Article
- Contribution of local regeneration of glucocorticoids to tissue steroid pools.The Journal of endocrinology · 2023Article
- Involvement of brain-derived neurotrophic factor signaling in the pathogenesis of stress-related brain diseases.Frontiers in molecular neuroscience · 2023Review
- 11β-HSD1 participates in epileptogenesis and the associated cognitive impairment by inhibiting apoptosis in mice.Journal of translational medicine · 2022Article
- Diabetes and associated cognitive disorders: Role of the Hypothalamic-Pituitary Adrenal axis.Metabolism open · 2022Review
- 11β-HSD as a New Target in Pharmacotherapy of Metabolic Diseases.International journal of molecular sciences · 2022Review
- Enhanced Angiogenesis by 11βHSD1 Blockage Is Insufficient to Improve Reperfusion Following Hindlimb Ischaemia.Frontiers in cardiovascular medicine · 2021Article
- 11β-HSD1 Inhibition Rescues SAMP8 Cognitive Impairment Induced by Metabolic Stress.Molecular neurobiology · 2020Article
- Is AD a Stress-Related Disorder? Focus on the HPA Axis and Its Promising Therapeutic Targets.Frontiers in aging neuroscience · 2019Article
- 11β-HSD1 Inhibition by RL-118 Promotes Autophagy and Correlates with Reduced Oxidative Stress and Inflammation, Enhancing Cognitive Performance in SAMP8 Mouse Model.Molecular neurobiology · 2018Article
- 11β-hydroxysteroid dehydrogenase-1 deficiency alters brain energy metabolism in acute systemic inflammation.Brain, behavior, and immunity · 2018Article
- Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids.Psychoneuroendocrinology · 2018Article
- Exploring N-acyl-4-azatetracyclo[5.3.2.0Molecules (Basel, Switzerland) · 2018Article
- Quantification of 11β-hydroxysteroid dehydrogenase 1 kinetics and pharmacodynamic effects of inhibitors in brain using mass spectrometry imaging and stable-isotope tracers in mice.Biochemical pharmacology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids (GCs) from intrinsically inert 11-keto substrates inside cells, including neurons, thus amplifying steroid action. Excess GC action exerts deleterious effects on the hippocampus and causes impaired spatial memory, a key feature of age-related cognitive dysfunction. Mice with complete deficiency of 11β-HSD1 are protected from spatial memory impairments with aging. Here, we tested whether lifelong or short-term decreases in 11β-HSD1 activity are sufficient to alter cognitive function in aged mice. Aged (24 months old) heterozygous male 11β-HSD1 knock-out mice, with ∼60% reduction in hippocampal 11β-reductase activity throughout life, were protected against spatial memory impairments in the Y-maze compared to age-matched congenic C57BL/6J controls. Pharmacological treatment of aged C57BL/6J mice with a selective 11β-HSD1 inhibitor (UE1961) for 10 d improved spatial memory performance in the Y-maze (59% greater time in novel arm than vehicle control). These data support the use of selective 11β-HSD1 inhibitors in the treatment of age-related cognitive impairments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.