Behavioral and omics analyses study on potential involvement of dipeptide balenine through supplementation in diet of senescence-accelerated mouse prone 8

Abstract

This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+WME) supplemented diet for 26weeks were subjected to four behavioral tests – open field, Y-maze, novel object recognition, and water-filled multiple T-maze – to examine effects on learning and memory. Brain transcriptome of SAMP8 mice-fed the WME diet over control low-safflower oil (LSO) diet-fed mice was delineated on a 4×44K mouse whole genome DNA microarray chip. Results revealed the WME diet not only induced improvements in the learning and memory formation but also positively modulated changes in the brain of the SAMP8 mouse; the gene inventories are publically available for analysis by the scientific community. Interestingly, the SAMP8 mouse model presented many genetic characteristics of AD, and numerous novel molecules (Slc2a5, Treh, Fbp1, Aldob, Ppp1r1a, DNase1, Agxt2l1, Cyp2e1, Acsm1, Acsm2, and Pah) were revealed over the SAMR1 (senescence-accelerated mouse resistant 1) mouse, to be oppositely regulated/recovered under the balenine (+WME) supplemented diet regime by DNA microarray and bioinformatics analyses. Our present study demonstrates an experimental strategy to understand the effects of dipeptide balenine, prominetly contained in meat diet, on SAMP8, providing new insight into whole brain transcriptome changes genome-wide. The gene expression data has been deposited into the Gene Expression Omnibus (GEO): GSE76459. The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation.