Experiment Id | E-GEOD-68515 | Series Id | GSE68515 |
Name | Hippocampal gene expression in aged and young HSD1 knockout mice | Experiment Type | transcription profiling by array |
Study Type | WT vs. Mutant | Source | ArrayExpress |
Curation Date | 2019-04-15 |
description | Mice deficient in the glucocorticoid-regenerating enzyme 11beta-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 11beta-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 11beta-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 11beta-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. 20 samples, 5 groups of 4 biological replicates each. Young, Wild Type animals are overall controls |