Perinatal Choline Supplementation Reduces Amyloidosis and Increases Choline Acetyltransferase Expression in the Hippocampus of the APPswePS1dE9 Alzheimer's Disease Model Mice.

Tiffany J Mellott,Jan K Blusztajn,Olivia M Huleatt,Sarah M Pender,Bethany N Shade,Barbara E Slack,Yi B Liu,Masuo Ohno

doi:10.1371/journal.pone.0170450

Abstract

Prevention of Alzheimer's disease (AD) is a major goal of biomedical sciences. In previous studies we showed that high intake of the essential nutrient, choline, during gestation prevented age-related memory decline in a rat model. In this study we investigated the effects of a similar treatment on AD-related phenotypes in a mouse model of AD. We crossed wild type (WT) female mice with hemizygous APPswe/PS1dE9 (APP.PS1) AD model male mice and maintained the pregnant and lactating dams 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. As compared to APP.PS1 mice reared on the control diet, the hippocampus of the perinatally choline-supplemented APP.PS1 mice exhibited: 1) altered levels of amyloid precursor protein (APP) metabolites–specifically elevated amounts of β-C-terminal fragment (β-CTF) and reduced levels of solubilized amyloid Aβ40 and Aβ42 peptides; 2) reduced number and total area of amyloid plaques; 3) preserved levels of choline acetyltransferase protein (CHAT) and insulin-like growth factor II (IGF2) and 4) absence of astrogliosis. The data suggest that dietary supplementation of choline during fetal development and early postnatal life may constitute a preventive strategy for AD.

Highlights

In the hippocampus of 12-month-old APP.PS1 mice, we measured the levels of the products of APP cleavage catalyzed by the α and β secretase enzymes, i.e. the α- and β-C-terminal fragments (CTFs) of APP. β-CTF is the substrate of γ secretase that produces the Aβ peptides
Using Western blot analysis with an antibody raised against the C-terminal end of APP (Fig 2), we found that, while choline supplementation had no effect on the α-CTF levels, it increased the levels of the β-CTF by approximately 30% as compared to controls in both females and males (Fig 2A and 2B)
Our data showing that perinatal choline supplementation increased the hippocampal levels of β-CTF in both sexes is consistent with this notion

Summary

Introduction

We have previously shown that high choline intake during gestation and perinatal period in rodent models prevents age-related memory decline [1] and in the current study we test the idea

Methods

Results

Conclusion