ID1201, the ethanolic extract of the fruit of Melia toosendan ameliorates impairments in spatial learning and reduces levels of amyloid beta in 5XFAD mice

Abstract

A previous study has demonstrated the anti-amyloidogenic effects of the ethanolic extract of Meliae Fructus (ID1201) using cell lines with stably expressed human Swedish mutant APP695 and β-secretase 1, and 5Xfamilial AD (FAD) mice carrying five mutations. Here, we investigated the effects of ID1201 on cognitive impairment in 5XFAD mice. Daily administration of ID1201 was commenced at 3 months of age and continued for 3 months. Mice were serially trained in cued/response and place/spatial training tasks in the Morris water maze. After this training, testing for strategy preference was conducted. Non-transgenic control mice with vehicle treatment, vehicle-treated 5XFAD, and ID1201-treated 5XFAD mice showed equivalent performance in cued/response training. However, as training progressed to the subsequent place/spatial learning, vehicle-treated control and ID1201-treated 5XFAD mice differed significantly from vehicle-treated 5XFAD mice in measures of spatial learning (search error and adaptive spatial learning strategy). In the strategy preference test that followed, control mice preferred a place/spatial strategy relative to vehicle-treated 5XFAD mice, but differences between ID1201-treated 5XFAD mice and vehicle-treated 5XFAD mice were not significant. Additionally, ID1201 treatment reduced hippocampal levels of insoluble Aβ42 and increased cortical levels of soluble amyloid precursor protein α. These results indicate that ID1201 may possess potential as a therapeutic agent for Alzheimer's disease by decreasing Aβ deposits.

Keywords: 5XFAD; Amyloid beta; Amyloid precursor protein; ID1201; Spatial memory.