Project description:The epigenetic landscape is vulnerable to variations in diet. Here, we investigated the influence of different PUFA dietary supplements on rodents’ nervous system development and functions and potential consequences for neurodegenerative disorders. We have previously studied the genomic plasticity of these biofunctions in mice fed on high n-3 PUFA enriched diet (ERD). In conjunction, in the present study, we introduced a second equicaloric diet with n-3 PUFA optimally balanced by n-6 PUFA (BLD). The typical lab diet with high n-6 PUFA was the baseline. Randomly grouped C57BL/6j mice were fed on any of these three diets from their neonatal age to late adolescent. Post-euthanasia, the transcriptomic landscape of hemibrains was investigated in parallel for two epigenetic mechanisms, namely the miRNA profile and DNA methylation. Integrating data we focused on those genes which had both hypermethylated CpG islands and silenced transcripts. Of these, 308 and 131 genes were perturbed by ERD and BLD, respectively, in comparison to the baseline. Also, miRNA:mRNA pairs were screened to identify those overexpressed miRNAs that silenced gene transcription. There were 18 and 39 miRNAs that met the cutoff in ERD- and BLD-fed mice, respectively. The majority of miRNAs overexpressed by BLD are associated with Alzheimer’s and schizophrenia. BLD allowed hypermethylation of those genes that enriched the networks associated with calcium-releasing neurotransmitters. Downstream networks leading to LTP, memory, cognition and learning were perturbed in sync. ERD permitted hypermethylation of genes that enrich the cytoskeletal development network and promote the formation of neuronal precursors. We present the conclusions taking into full account the limited knowledge regarding the epigenetic influence on biofunctions. Since this study has single time point, we could not verify if these functional attributes are the cause or the consequences of epigenetic plasticity. Hence, a more comprehensive study in this regard is essential.

Project description:in the present study, we evaluated whether microbiota modulation is able to restore hepatic steatosis induced by n-3 PUFA depletion in mice. For this purpose, mice were fed during three months with a n-3 PUFA-depleted diet (presenting a high n-6/n-3 PUFA ratio), and then supplemented with fructooligosaccharides (FOS, 0.25g/day/mice), a prebiotic, during the last ten days of the experiment (DEF/FOS). In the same time, some n-3 PUFA-depleted mice were returned on a control diet during the last 10 days of treatment (DEF/CT) to compare the effect of FOS supplementation to a restored intake in n-3 PUFA. Microarray analyses were performed to identify the molecular targets modified by FOS supplementation in the liver of n-3 PUFA depleted mice. These mice were compared to control mice (fed a control diet during the 112 days of experiment) and to n-3 PUFA-depleted mice (fed a n-3 PUFA-depleted diet during the 112 days of experiment) for which the results have been previously published (Pachikian B.D. et al. PLoS One. 2011;6(8):e23365, accession number GSE26986) Male C57Bl/6J mice (9 weeks old; Charles River, Brussels, Belgium) were housed in groups of 4 mice per cage at 22Â°C in a 12 h light/dark cycle and given free access to diet and water. After an acclimatisation period of 1 week, mice were fed a control (CT) (D08041805, Research Diets, New Brunswick, USA) or an n-3 PUFA-depleted diet (DEF) (D08041806, Research Diets, New Brunswick, USA) for 112 days ad libitum. The CT diet contained the following (percent w/w): casein 20, total carbohydrate 72.4 (including corn starch 44.2, sucrose 10, maltodextrin 13.2, cellulose 5), soybean oil 5, mineral mix 3.5 and vitamin mix 1. The depletion was induced by replacing the soybean oil with sunflower oil, which exhibited a higher n-6/n-3 PUFA ratio. The n-6/n-3 PUFA ratio was 6.9 and 127.2 for the CT diet and the DEF diet, respectively. Ten days before the end of the experiment, DEF mice were divided into three groups: DEF, DEF/FOS and DEF/CT mice. The DEF mice were still fed with the n-3 PUFA depleted diet (DEF). The DEF/FOS mice were still fed the DEF diet and were supplemented for 10 days with fructooligosaccharides (DEF/FOS). FOS (Beneo P95 gift from Orafti; Tienen, Belgium) was added to tap water in a concentration adequate to reach an intake of 0.25g of FOS per day. For DEF/CT mice, the DEF diet was replaced by the CT diet during the last 10 days of treatment. At the end of the study period, mice fed the CT (n=4), DEF (n=7), DEF/CT (n=8) or DEF/FOS diet (n=8) were anaesthetised (ketamine/xylazine i.p., 100 and 10 mg/kg of body weight, respectively). The liver tissue was immediately clamped in liquid N2 and kept at -80Â°C until analysis. All mice experiments were approved by the local animal ethics committee and the housing conditions were as specified by the Belgian Law of April 6, 2010 on the protection of laboratory animals (agreement nÂ° LA 1230314).

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Contribution of Poly-unsaturated Fatty Acids on Cerebral Neurobiology: An Integrated Omics Approach with Epigenomic Focus [Agilent]

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