MicroRNA expression profiling in the prefrontal cortex: Putative mechanisms for the cognitive effects of adolescent high fat feeding

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Date
2018-05-29Type
- Journal Article
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Abstract
The medial prefrontal cortex (mPFC), master regulator of higher-order cognitive functions, is the only brain region that matures until late adolescence. During this period, the mPFC is sensitive to stressful events or suboptimal nutrition. For instance, high-fat diet (HFD) feeding during adolescence markedly impairs prefrontal-dependent cognition. It also provokes multiple changes at the cellular and synaptic scales within the mPFC, suggesting that major transcriptional events are elicited by HFD during this maturational period. The nature of this transcriptional reprogramming remains unknown, but may include epigenetic processes, in particular microRNAs, known to directly regulate synaptic functions. We used high–throughput screening in the adolescent mouse mPFC and identified 38 microRNAs differentially regulated by HFD, in particular mir-30e-5p. We used a luciferase assay to confirm the functional effect of mir-30e-5p on a chosen target: Ephrin-A3. Using global pathway analyses of predicted microRNA targets, we identified biological pathways putatively affected by HFD. Axon guidance was the top-1 pathway, validated by identifying gene expression changes of axon guidance molecules following HFD. Our findings delineate major microRNA transcriptional reprogramming within the mPFC induced by adolescent HFD. These results will help understanding the contribution of microRNAs in the emergence of cognitive deficits following early-life environmental events. Show more
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https://doi.org/10.3929/ethz-b-000268873Publication status
publishedExternal links
Journal / series
Scientific ReportsVolume
Pages / Article No.
Publisher
Nature Publishing GroupFunding
146217 - Inflammation-mediated epigenetic priming of neurodevelopmental disease (SNF)
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Citations
Cited 10 times in
Web of Science
Cited 11 times in
Scopus
ETH Bibliography
yes
Altmetrics