Mechanism Of Sodium Selenate On Alzheimer’s Disease Investigated By Translatomics And Multiple Reaction Monitoring

Alzheimer’s disease(AD)is a progressive neurodegenerative disease,widely distributed in elder people.The potential therapeutic effect of sodium selenate on the triple transgenic AD model mouse(3xTg-AD)has been reported previously.However,only the changes of AD hallmark and their related pathways have been studied as limited by the traditional biochemical assays.Translatomics techniques and multi-reactions monitoring(MRM)in mass spectrometry have never been applied to the study of the effects of selenate on AD.Compared with transcriptome that sequences the total mRNA,translatomics detects the sequence of mRNA being translated on ribosome only,which may be more representative of the protein levels.And compare with proteome,translatomics can detects extrame low abundant proteins,which provide new methods to discover new AD biomarker.Western blot and ELISA are commonly used for the validation of differentially expressed genes,but these methods are often limited to certain antibodies and kits.MRM in mass spectrometry automatically detects dozens or hundreds of peptides at one time,without antibody and lots of manual operation required.In this study,the reliefing effects of three compounds including cyclodextrin,selenocyclodextrin and sodium selenate were tested in cell models.Translatomics was applied to study the regulation of sodium selenate on the mRNA translation in the cortex of 3xTg-AD mice,and then MRM was used to verify the differentially expressed genes at protein levels.Our results showed that sodium selenate,among all compounds,can significantly improve cell viability.Then the 3xTg-AD mice were fed with 3μM sodium selenate in drinking water from 3 monthold to 6 month-old.The cortex tissues were collected for translatomics and MRM study.Our translatomics study revealed 65 differentially expressed genes(32 down-regulated and 33 up-regulated)between AD and selenate treated AD groups,including NADH dehydrogenase(ubiquinone),alpha 1,cytochrome c oxidase subunit 7A,39 S ribosomal protein L53 and romol.The Kyoto encyclopedia of genes and genomes(KEGG)pathway and gene ontology(GO)enrichment analysis showed that most of the differentially expressed genes were distributed in pathways of mitochondrial respiratory complex assembly and organellar ribosome.Our MRM analyses shows that including solute carrier family 6 member 17,hexokinase 1,cytochrome c,7 protein up-regulated between AD and WT groups.And in the comparison of AD and selenate treated AD groups,hexokinase 1,cyclin-dependent-like kinase 5,protein kinase C delta up-regulated.These results indicated that the therapeutic effect of sodium selenate on AD was mainly through restoring the oxidative respiratory chain and ribosome composition.In conclusion,sodium selenate may be a potential treatment to alleviate AD.