RT Journal Article SR Electronic T1 11β-Hydroxysteroid Dehydrogenase Type 1 Expression Is Increased in the Aged Mouse Hippocampus and Parietal Cortex and Causes Memory Impairments JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6916 OP 6920 DO 10.1523/JNEUROSCI.0731-10.2010 VO 30 IS 20 A1 Megan C. Holmes A1 Roderick N. Carter A1 June Noble A1 Shruti Chitnis A1 Amy Dutia A1 Janice M. Paterson A1 John J. Mullins A1 Jonathan R. Seckl A1 Joyce L. W. Yau YR 2010 UL http://www.jneurosci.org/content/30/20/6916.abstract AB Increased neuronal glucocorticoid exposure may underlie interindividual variation in cognitive function with aging in rodents and humans. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the regeneration of active glucocorticoids within cells (in brain and other tissues), thus amplifying steroid action. We examined whether 11β-HSD1 plays a role in the pathogenesis of cognitive deficits associated with aging in male C57BL/6J mice. We show that 11β-HSD1 levels increase with age in CA3 hippocampus and parietal cortex, correlating with impaired cognitive performance in the water maze. In contrast, neither circulating corticosterone levels nor tissue corticosteroid receptor expression correlates with cognition. 11β-HSD1 elevation appears causal, since aging (18 months) male transgenic mice with forebrain-specific 11β-HSD1 overexpression (∼50% in hippocampus) exhibit premature age-associated cognitive decline in the absence of altered circulating glucocorticoid levels or other behavioral (affective) deficits. Thus, excess 11β-HSD1 in forebrain is a cause of as well as a therapeutic target in memory impairments with aging.