Contributions of polyunsaturated fatty acids (PUFA) on cerebral neurobiology: an integrated omics approach with epigenomic focus.
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.
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; The Geneva Foundation, Tacoma, WA, USA 98402.
Nabarun
N
Chakraborty
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; The Geneva Foundation, Tacoma, WA, USA 98402.
Seid
S
Muhie
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD, USA 21702.
Raina
R
Kumar
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010.
Aarti
A
Gautam
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; The Geneva Foundation, Tacoma, WA, USA 98402.
Seshamalini
S
Srinivasan
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; The Geneva Foundation, Tacoma, WA, USA 98402.
Bintu
B
Sowe
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD, USA 21702.
George
G
Dimitrov
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010; The Geneva Foundation, Tacoma, WA, USA 98402.
Stacy-Ann
SA
Miller
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010.
Marti
M
Jett
Integrative Systems Biology, US Army Center for Environmental Health Research, Frederick, MD, USA 21702-5010. Electronic address: Rasha.Hammamieh1.civ@mail.mil.
Rasha
R
Hammamieh
D000818:Animals; D018899:CpG Islands; D019175:DNA Methylation; D019587:Dietary Supplements; D044127:Epigenesis, Genetic / Q000187:drug effects; D057890:Epigenomics / Q000379:methods; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs; D012333:RNA, Messenger
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D035683:MicroRNAs; D012333:RNA, Messenger