Investigating the significance of 11β-HSD type 1 in the ageing brain

• Main Author: Hibberd, Carina Jayne
• Published: University of Edinburgh 2005
• Subjects: 612.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652411

In-situ-hybridisation of the mouse hippocampus and cerebellum, showed no changes in 11β-HSD1 mRNA with ageing. However, decreases in mRNA of corticosteroid receptors indicated a possible, neuro-protective mechanisms through changes in GC signalling. The improved ageing in a hippocampal –dependent behavioural task, was further investigated on a C57BL/6 background. Middle-aged mice showed improved long-term memory in a Y-maze spatial learning test, with no differences in short-term or working memory. In light of the GC role in anxiety and exploration, the elevated-plus-maze and open-field were investigated. There were no definitive differences in visits to arms of the elevated-plus-maze, but an increase in risk assessment suggested increased anxiety in the young Ko (<i>vs</i> young control). The young Ko were more active than the young control in the open-field, exploring the outer zone proportionally more than young control, again suggesting increased anxiety, certainly behavioural activation. The significance of enzyme expression in the cerebellum was explored using a motor-learning task. Over 5 days of learning, the young Ko were impaired compared with young controls and there was a negative effect of age. Although, 11β-HSD1 has been shown as a reductase in hippocampal neurons, there remains some debate over the activity direction in other cells of the brain. To address this, activity was measured in primary, cultured cells from brain regions of interest. No significant activity was found in cells from the frontal cortex, but cerebellar granular neurons showed reductase activity comparable with hippocampal cultures.