The effects of perinatal choline supplementation on the cognitive function of the APPNL-G-F mouse model of Alzheimer’s disease

• Main Author: Laguna-Torres, Jessenia Yaris
• Other Authors: Mellott, Tiffany J.
• Language: en_US
• Published: 2021
• Subjects: Pathology
• Online Access: https://hdl.handle.net/2144/43441

Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies, this laboratory demonstrated that high intake of the essential nutrient, choline, during gestation ameliorated hippocampal amyloidosis in hemizygous APPswe/PS1dE9 (APP.PS1) AD model mice. In this study we investigated the effects of a similar treatment on behavioral phenotypes in the APPNL-G-F mouse model for AD. These mice express a humanized APP with three mutations that cause familial AD in humans [Swedish (NL), Arctic (G), and Beyreuther/Iberian (F)] under the control of the endogenous mouse APP promotor. The latter permits to overcome problems related to the overexpression of APP observed in the transgenic mouse models (e.g. APP.PS1) and is therefore considered a more physiological model for AD well suited for studies of the pathophysiology of this disease. We maintained the pregnant and lactating wild type C57BL/6J control mice and homozygous APPNL-G-F mice on a control AIN76A diet containing 1.1 g/kg of choline or a choline-supplemented (5 g/kg) diet. After weaning all offspring consumed the control diet. We used the male and female APPNL-G-F offspring as the AD model and the wild type mice as controls. The animals were examined in a cross-sectional fashion at 3, 6, 9 and 12 months of age using the Open Field (OF), Elevated Plus Maze (EPM), Barnes Maze (BM), and Contextual Fear Conditioning (CFC) experimental paradigms. As compared to controls, the APPNL-G-F mice exhibited abnormalities in anxiety-related behaviors at 3 and 6 months of age and learning and memory deficits at 9 and 12 months of age. Perinatal choline supplementation ameliorated some of the memory deficits in the 12-month old APPNL-G-F mice observed in the CFC test. The data suggest that dietary supplementation with choline during fetal development and early postnatal life prevents some of the behavioral abnormalities in the APPNL-G-F AD model mice.