Contributions of polyunsaturated fatty acids (PUFA) on cerebral neurobiology: an integrated omics approach with epigenomic focus

Abstract The epigenetic landscape is vulnerable to diets. Here, we investigated the influence of different polyunsaturated fatty acids (PUFA) dietary supplements on rodents' nervous system development and functions and potential consequences to neurodegenerative disorders. Our previous nutrigenomics study showed significant impact of high n-3 PUFA-enriched diet (ERD) on synaptogenesis and various neuromodulators. The present study introduced a second equicaloric diet with n-6 PUFA balanced by n-3 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline. Transcriptomic and epigenetic investigations, namely microRNA (miRNA) and DNA methylation assays, were carried out on the hemibrains of the C57BL/6j mice fed on any of these three diets from their neonatal age to midlife. Integrating the multiomics data, we focused on the genes encoding both hypermethylated CpG islands and suppressed transcripts. In addition, miRNA:mRNA pairs were screened to identify those overexpressed miRNAs that reduced transcriptional expressions. The majority of miRNAs overexpressed by BLD are associated with Alzheimer's and schizophrenia. BLD implicated long-term potentiation, memory, cognition and learning, primarily via hypermethylation of those genes that enrich the calcium-releasing neurotransmitters. ERD caused hypermethylation of those genes that enrich cytoskeletal development networks and promote the formation of neuronal precursors. We drew the present observations in light of our limited knowledge regarding the epigenetic influences on biofunctions. A more comprehensive study is essential to understand the broad influences of dietary supplements and to suggest optimal dietary solutions for neurological disorders.