Explorer Decreased Npas 4 and Arc mRNA levels in the hippocampus of aged memory - impaired wild type but not memory preserved 11 - HSD 1 deficient mice

Decreased Npas4 and Arc mRNA levels in the hippocampus of aged memory-impaired wild type but not memory preserved 11-HSD1 deficient mice 'Decreased Npas4 and Arc mRNA levels in the hippocampus of aged memory-impaired wild type but not memory preserved 11-HSD1 deficient mice' General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Decreased Npas4 and Arc mRNA levels in the hippocampus of aged memory-impaired wild type but not memory preserved 11β-HSD1 deficient mice Short title: 11β-HSD1-deficiency and ageing alters Npas4 and Arc mRNA Abstract Mice deficient in the glucocorticoid-regenerating enzyme 11β-HSD1 resist age-related spatial memory impairment. To investigate the mechanisms/pathways involved, we used microarrays to identify differentially expressed hippocampal genes that associate with cognitive ageing and 11β-HSD1. Aged wild-type mice were separated into memory-impaired and unimpaired relative to young controls according to their performance in the Y-maze. All individual aged 11β-HSD1-deficient mice showed intact spatial memory. The majority of differentially expressed hippocampal genes were increased with ageing (e.g. immune/inflammatory response genes) with no genotype differences. However, the neuronal-specific transcription factor, Npas4 and immediate early gene, Arc were reduced (relative to young) in the hippocampus of memory-impaired but not unimpaired aged wild-type or aged 11β-HSD1-deficient mice. Quantitative RT-PCR and in situ hybridization confirmed reduced Npas4 and Arc mRNA expression in memory-impaired aged wild-type mice. These findings suggest that 11β-HSD1 may contribute to the decline in Npas4 and Arc mRNA levels associated with memory impairment during ageing, and that decreased activity of synaptic plasticity pathways involving Npas4 and Arc may, in part, underlie the memory deficits seen in cognitively-impaired aged wild-type mice.