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Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammati...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022082/ https://www.ncbi.nlm.nih.gov/pubmed/27529677 http://dx.doi.org/10.1038/tp.2016.136 |
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author | Wei, Y B Liu, J J Villaescusa, J C Åberg, E Brené, S Wegener, G Mathé, A A Lavebratt, C |
author_facet | Wei, Y B Liu, J J Villaescusa, J C Åberg, E Brené, S Wegener, G Mathé, A A Lavebratt, C |
author_sort | Wei, Y B |
collection | PubMed |
description | Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms. |
format | Online Article Text |
id | pubmed-5022082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50220822016-09-19 Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression Wei, Y B Liu, J J Villaescusa, J C Åberg, E Brené, S Wegener, G Mathé, A A Lavebratt, C Transl Psychiatry Original Article Elevation of the proinflammatory cytokine IL-6 has been implicated in depression; however, the mechanisms remain elusive. MicroRNAs (miRNAs) are small non-coding RNAs that inhibit gene expression post-transcriptionally. The lethal-7 (let-7) miRNA family was suggested to be involved in the inflammation process and IL-6 was shown to be one of its targets. In the present study, we report elevation of Il6 in the prefrontal cortex (PFC) of a genetic rat model of depression, the Flinders Sensitive Line (FSL) compared to the control Flinders Resistant Line. This elevation was associated with an overexpression of LIN28B and downregulation of let-7 miRNAs, the former an RNA-binding protein that selectively represses let-7 synthesis. Also DROSHA, a key enzyme in miRNA biogenesis was downregulated in FSL. Running was previously shown to have an antidepressant-like effect in the FSL rat. We found that running reduced Il6 levels and selectively increased let-7i and miR-98 expression in the PFC of FSL, although there were no differences in LIN28B and DROSHA expression. Pri-let-7i was upregulated in the running FSL group, which associated with increased histone H4 acetylation. In conclusion, the disturbance of let-7 family biogenesis may underlie increased proinflammatory markers in the depressed FSL rats while physical activity could reduce their expression, possibly through regulating primary miRNA expression via epigenetic mechanisms. Nature Publishing Group 2016-08 2016-08-16 /pmc/articles/PMC5022082/ /pubmed/27529677 http://dx.doi.org/10.1038/tp.2016.136 Text en Copyright © 2016 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Wei, Y B Liu, J J Villaescusa, J C Åberg, E Brené, S Wegener, G Mathé, A A Lavebratt, C Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title | Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title_full | Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title_fullStr | Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title_full_unstemmed | Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title_short | Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
title_sort | elevation of il6 is associated with disturbed let-7 biogenesis in a genetic model of depression |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5022082/ https://www.ncbi.nlm.nih.gov/pubmed/27529677 http://dx.doi.org/10.1038/tp.2016.136 |
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