MicroRNA Profiling in the Medial and Lateral Habenula of Rats Exposed to the Learned Helplessness Paradigm: Candidate Biomarkers for Susceptibility and Resilience to Inescapable Shock

PLoS One. 2016 Aug 5;11(8):e0160318. doi: 10.1371/journal.pone.0160318. eCollection 2016.


Depression is a highly heterogeneous disorder presumably caused by a combination of several factors ultimately causing the pathological condition. The genetic liability model of depression is likely to be of polygenic heterogeneity. miRNAs can regulate multiple genes simultaneously and therefore are candidates that align with this model. The habenula has been linked to depression in both clinical and animal studies, shifting interest towards this region as a neural substrate in depression. The goal of the present study was to search for alterations in miRNA expression levels in the medial and lateral habenula of rats exposed to the learned helplessness (LH) rat model of depression. Ten miRNAs showed significant alterations associating with their response to the LH paradigm. Of these, six and four miRNAs were significantly regulated in the MHb and LHb, respectively. In the MHb we identified miR-490, miR-291a-3p, MiR-467a, miR-216a, miR-18b, and miR-302a. In the LHb miR-543, miR-367, miR-467c, and miR-760-5p were significantly regulated. A target gene analysis showed that several of the target genes are involved in MAPK signaling, neutrophin signaling, and ErbB signaling, indicating that neurotransmission is affected in the habenula as a consequence of exposure to the LH paradigm.

MeSH terms

  • Animals
  • Body Weight
  • Electroshock
  • Gene Expression Profiling
  • Genetic Markers
  • Habenula / physiology*
  • Helplessness, Learned*
  • Male
  • MicroRNAs / genetics*
  • Rats, Sprague-Dawley


  • Genetic Markers
  • MicroRNAs

Grants and funding

The study was funded by the Lundbeck Foundation (R77-A7085). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.