Abstract:
Large arteries stiffen due to advancing age and they are associated with cognitive impairment. However, the direct effects of long-term large artery stiffness require further investigation. Therefore, we studied cognitive and cerebral artery function in a model of greater large artery stiffness, the elastin haploinsufficient (Eln+/-) mouse, at old age. We examined old wildtype (Eln+/+, n=8, 25 mo), old Eln+/- (n=8, 25 mo), and young wildtype (YC, n=9, 7 mo) mice. Memory was tested through the Morris Water Maze (MWM) test and motor coordination was measured through the accelerating Rotarod test. Endothelial function was measured in ex vivo pressurized posterior cerebral arteries (PCAs) by dilation to acetylcholine (ACh). In the MWM test, old Eln+/- mice crossed the target area fewer times than old Eln+/+ mice (p<0.05), indicating impaired spatial memory. In the accelerating Rotarod test, old Eln+/- mice stayed on the rod for less time than the old Eln+/+ and young mice (p<0.05), suggesting poor motor coordination. Maximal PCA dilation to ACh was lower in old Eln+/- mice compared to old Eln+/+ and young mice (p<0.01), indicating impaired endothelial function. These results indicate that long-term exposure to large artery stiffness leads to impaired spatial memory, motor coordination, and cerebral artery endothelial function. Future research is needed to study the cellular mechanisms resulting from large artery stiffness.
