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Contribution of Poly‐unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus
Author(s) -
Chakraborty Nabarun,
Muhie Seid,
Gautam Aarti,
Hammamieh Rasha,
Jett Marti
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.628.5
Subject(s) - epigenomics , microrna , transcriptome , gene silencing , biology , schizophrenia (object oriented programming) , fish oil , neuroprotection , cancer research , dna methylation , neuroscience , bioinformatics , medicine , biochemistry , gene , gene expression , psychiatry , fish <actinopterygii> , fishery
Our previous transcriptomic study [1] suggested potential positive significance of the effects of fish oil on the cerebralneurogenesis and neuroprotection, and contrasting therapeutic implications for the neurodegenerative disorders. Stimulating the calcium‐induced growth cascade and downstream PI3K‐AKT‐PKC network, fish oil augmented neuritogenesis, reinforced synapse and potentially promoted long‐term potentiation. In conjunction, this diet reduced the amyloidal burden, attenuated oxidativestress, and assisted in somatostatin activation. Therefore, we anticipated the potential therapeutic roles of fish oil in attenuating Alzheimer's disease, Parkinson's disease, and affective disorder. Motivated from this past study, we investigated the shift of the DNA methylation and microRNA profiles caused by these same dietary supplements and potential consequences on cerebralfunctionalities. N‐3 PUFA‐enriched diet (ERD, n3:n6= 7:1) and balanced diet (BLD, n3:n6= 1:1) were customized to contain caloric content equivalent to the standard lab diet (STD, n3:n6= 1:6). The diets were administered to three groups of C57BL/6J male mice from their weaning age until late adolescence. At the study endpoint, the transcriptomic and epigenomic profiles of the hemi brains were probed. Our primary focus was on hypermethylated probes and microRNAs which were causally related to transcriptional silencing. We found 18 overexpressed microRNAs in the ERD‐fed mice that inhibited the transcriptional expressions of 580 genes.. Likewise, there were 40 overexpressed microRNAs targeting 800 suppressed gene in BLD‐fed mice; a majority of these microRNAs are functionally associated with the neurodegenerative disorders, such as schizophrenia and Alzheimer's disease. In addition, there were ~4,000 probes hypermethylated in either ERD‐ or BLD‐fed mice. Of particular interest, ERD‐fed mice exhibited ~300 genes concurrently imprinting hypermethylated CpG islands and silenced transcripts. Similarly, 131 genes displayed hypermethylated CpG islands and transcriptional suppression in BLD‐fed mice. All these hypermethylated CpG islands were mapped within 50kb from their respective transcriptional startsites, indicating their rather archetypal effects on transcriptional silencing. Functional annotation of these genes indicated a pattern of neurological implications distinguishing the positive effects related to ERD and BLD. ERD primarily influenced the developmental phase of neuronal and cerebral activation, while the behavioral manifestations were potentially stimulated by BLD. A validation study is underway. Disclaimer: Research was conducted in compliance with the Animal Welfare Act, and all other Federal requirements. The views expressed are those of the authors and do not constitute endorsement by the U.S. Army.