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Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression

Y B Wei1,2, J J Liu1,2, J C Villaescusa2,3

  • 1Neurogenetics Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Translational Psychiatry
|August 17, 2016
PubMed

Insights

Depression is linked to increased inflammation, potentially involving microRNAs (miRNAs). Running may reduce inflammation in depressed rats by restoring let-7 miRNA levels, possibly through epigenetic changes.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Elevated interleukin-6 (IL-6), a proinflammatory cytokine, is implicated in depression, but underlying mechanisms are unclear.
  • MicroRNAs (miRNAs) regulate gene expression post-transcriptionally, and the let-7 miRNA family has been linked to inflammation, with IL-6 as a potential target.
  • LIN28B and DROSHA are key regulators of miRNA biogenesis and expression.

Purpose of the Study:

  • To investigate the role of let-7 miRNAs and their regulatory proteins in a genetic rat model of depression.
  • To examine the effects of running, a known antidepressant-like intervention, on IL-6, let-7 miRNAs, and related regulatory factors in the prefrontal cortex (PFC).

Main Methods:

  • Comparison of IL-6, LIN28B, DROSHA, and let-7 miRNA expression in the PFC of Flinders Sensitive Line (FSL) rats (depressed model) and Flinders Resistant Line (FRL) rats (control).
  • Analysis of these factors in FSL rats after an intervention of voluntary running.
  • Assessment of pri-let-7i and histone H4 acetylation levels.

Main Results:

  • FSL rats exhibited elevated IL-6, LIN28B, and reduced let-7 miRNAs and DROSHA in the PFC compared to FRL rats.
  • Running intervention in FSL rats decreased IL-6 levels and increased let-7i and miR-98 expression, without altering LIN28B or DROSHA.
  • Running was associated with increased pri-let-7i and histone H4 acetylation in the PFC of FSL rats.

Conclusions:

  • Dysregulation of let-7 miRNA biogenesis may contribute to elevated proinflammatory markers in this genetic depression model.
  • Physical activity (running) may ameliorate depression-related inflammation by modulating let-7 miRNA expression, potentially via epigenetic regulation of pri-miRNA.

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