β-ALANYL-3-METHYL-L-HISTIDINE, ANSERINE, AMELIORATES COGNITIVE DEFICITS IN AGED APPSWE/PSEN1DE9 ALZHEIMER’S DISEASE MODEL MOUSE THROUGH THE IMPROVEMENT OF BLOOD VESSEL DYSFUNCTION AS WELL AS GLIAL NEUROINFLAMMATORY REACTIONS

Abstract

We have recently discovered that a formula containing imidazole dipeptides improve cognitive functions of healthy elderly people. In this study, we tested whether anserine would improve the cognitive declines in aged AD model mice. In addition, to elucidate the effect of anserine on the AD model mouse, we investigated the blood vessel dysfunction as well as the glial neuroinflammatory reactions occurred in aged AD model mice. B6C3-Tg (APPswe/PSEN1dE9) 85Dbo/J AD model transgenic mouse was used in this study. We prepared the two groups of aged AD model mice for the anserine and placebo treated group. To assess the effect of anserine for the memory function, we performed the Morris Water Maze (MWM) test. The levels of Aβ accumulations in the hippocampus were evaluated by histochemical staining and ELISA. In AD model mice, inflammation often appears inducing the glial neuroinflammatory reactions and the dysfunction of the blood vessel system. To evaluate the extent of the glial inflammatory reactions, we performed immunostaining for astrocytes and microglia. The amount of inflammatory cytokine IL-1β was compared between the two groups by ELISA. To evaluate the blood vessels dysfunction, we used tomato lectin and anti-PDGFR-β to visualize the vascular endothelial cells and the capillary pericytes, respectively. In the probe test of the MWM, the memory decline was recovered by the treatment of anserine. Anserine had no effect on the formation of the senile plaques and the accumulation of Aβ1–42. Whereas, the decrease of the expression of astrocyte and inflammatory cytokine IL-1β was detected in the anserine treated group. An increasing coverage rate of pericyte was observed in the anserine treatment group. This data indicated that the anserine treatment protected blood vessel system of AD model mouse brain and then suppressed the neuroinflammation in the brain of AD model mouse. The administration of anserine in the aged AD model mice showed the improvement of the cognitive declines. The anserine treatment showed the improvement toward blood vessel dysfunction as well as glial neuroinflammatory reactions. Through these favorable functions, it is possible that the treatment of anserine may contribute to the improvement of the cognitive functions of AD patients.