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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(More)
In aging humans and rodents, inter-individual differences in cognitive function have been ascribed to variations in long-term glucocorticoid exposure. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) regenerates the active glucocorticoid cortisol from circulating inert cortisone, thus amplifying intracellular glucocorticoid levels in some tissues.(More)
Local brain amplification of glucocorticoids (GCs) by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays a pivotal role in age-related memory deficits. 11β-HSD1 deficient mice are protected from spatial memory impairments with aging, but the underlying mechanisms are unknown. To determine which brain receptors [high-affinity mineralocorticoid(More)
Glucocorticoids are pivotal in the maintenance of memory and cognitive functions as well as other essential physiological processes including energy metabolism, stress responses, and cell proliferation. Normal aging in both rodents and humans is often characterized by elevated glucocorticoid levels that correlate with hippocampus-dependent memory(More)
Increased neuronal glucocorticoid exposure may underlie interindividual variation in cognitive function with aging in rodents and humans. 11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the regeneration of active glucocorticoids within cells (in brain and other tissues), thus amplifying steroid action. We examined whether 11beta-HSD1(More)
The mechanisms by which antidepressants regulate the hypothalamic-pituitary-adrenal (HPA) axis are still unknown. The ABCB1-type multiple drug resistance (MDR) p-glycoprotein (PGP) regulates the HPA axis by limiting the access of glucocorticoids to the brain in mice and humans. Previous work in cell cultures has found that antidepressants enhance(More)
INTRODUCTION Studies have found that people with Multiple Sclerosis experience relatively high rates of anxiety and depression. Although methodologically robust, many of these studies had access to only modest sample sizes (N<200). The aims of this study were to use responses gained via the web portal of the UK MS Register (N>4000) to: describe the(More)
The effects of two different polymeric wound dressings and a new collagen matrix (CM) implant on the healing and scarring of full-thickness excision wounds were studied in swine. The synthetic polymers comprised an occlusive O2-impermeable hydrocolloid dressing (HCD) and an occlusive O2-permeable polyurethane film (PUF). The CM implant consisted of an(More)
As rats age, a subgroup will show spatial memory impairments, along with decreased corticosteroid receptors (MR and/or GR) in the hippocampus and a hyperactive hypothalamic-pituitary-adrenal axis. In previous work, we have shown that amitriptyline treatment increases hippocampal MR mRNA and improves spatial memory in young rats but had no effect in aged(More)
Increasing evidence links chronically elevated glucocorticoid levels and cognitive impairments in a subpopulation of aged rodents and humans. Antidepressant drugs improve hypothalamic-pituitary-adrenal axis feedback regulation and reduce plasma glucocorticoid levels. Decreasing the cumulative lifetime exposure to glucocorticoid excess by long-term exposure(More)