Effects Of Calorie Restriction On Neural Behaviors And Brain Proteome In Transgenic Mice With Alzheimer's Disease

Objective: Alzheimer's disease(AD),also termed dementia,is one of the most common neurodegenerative disease.With the aging of the population,the onset of AD is dramatically increased.Calorie restriction(CR)is a kind of dietary restriction,but it does not cause malnutrition.In numerous intervening measures of AD,CR shows its multiple powerful advantages in improvement of neurodegeneration.The purpose of this study is to explore the effects of calorie restriction on behavioral abmormalties and brain proteome in 3x Tg-AD mice.This study would be expected to provide scientific basis for the prevention and treatment of AD.Methods: In this study,we selected the triple transgenic AD(3x Tg-AD)mice and wild type(WT)mice as treated group that were assigned to the dietary regimen of 40% CR,and the control group were given to the dietary regimen of ad libitum(AL).First of all,the open field test,elevated plus-maze test and the light/dark box test were employed to evaluate the effects of CR on anxiety behavior;the forced swimming test and tail suspension test were employed to evaluate the effects on depression behavior;and the Morris water maze was employed to evaluate the effects on memory impairment.Then,we used two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)coupled with MALDL-TOF-MS to explore the effects of CR on the hippocampal proteome in the mice.Western-blot analysis was used to validate the the expression of some differential proteins.Results: Behavioral tests showed that CR could alleviate anxiety,depression and memory impairment of 3x Tg-AD mice.Proteomics analysis revealed a total of 11 differentially expressed proteins in hippocampus in WT mice with or without CR treatment;a total of 30 differentially expressed proteins in 3x Tg-AD mice compared with the WT mice;a total of 13 differentially expressed proteins in 3x Tg-AD mice with or without CR treatment.Bioinformatics analysis showed that these differentially expressed proteins were related to metabolic process,apoptosis process,biological regulation and others,and multiple abnormal expressed proteins that were closely related to the development and progression of AD.Among these differentially expressed proteins,synapse-associated protein synapsin-2(SYN2)and molecular chaperone 14-3-3 protein epsilon(14-3-3E)were verified by Western-blot analysis.Conclusion: Take together,our data suggested that CR could alleviate anxiety,depression and memory impairment of 3x Tg-AD mice,and the expression change of the molecules such as SYN2 and 14-3-3E by CR may be involved in the neuroprotective processes of CR.