Molecular profiling of the lateral habenula in a rat model of depression

PLoS One. 2013 Dec 5;8(12):e80666. doi: 10.1371/journal.pone.0080666. eCollection 2013.

Abstract

Objective: This study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level.

Methods: Rat whole genome expression chips (Affymetrix) were used to detect gene expression regulations in the lateral habenula of rats subjected to chronic mild stress (mild stressors exchanged twice a day for 8 weeks). Some rats received antidepressant treatment during fifth to eights week of CMS. The lateral habenula gene expression profile was studied through the gene ontology and signal pathway analyses using bioinformatics. Real-time quantitative polymerase chain reaction (RT-PCR) was used to verify the microarray results and determine the expression of the Fcrla, Eif3k, Sec3l1, Ubr5, Abca8a, Ankrd49, Cyp2j10, Frs3, Syn2, and Znf503 genes in the lateral habenula tissue.

Results: In particular we found that stress and antidepressant treatment affected intracellular cascades like growth factor receptor signaling, G-protein-coupled receptor signaling, and Wnt signaling - processes involved in the neuroplastic changes observed during the progression of depression and antidepressant treatment.

Conclusion: The present study suggests an important role of the lateral habenula in the development of depression-like conditions and correlates to previous studies demonstrating a significant role of the lateral habenula in depressive-like conditions and antidepressant treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anhedonia / drug effects
  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Cluster Analysis
  • Depression / complications
  • Depression / drug therapy*
  • Depression / genetics*
  • Depression / psychology
  • Disease Models, Animal
  • Eating / drug effects
  • Gene Expression Profiling
  • Habenula / drug effects*
  • Habenula / metabolism*
  • Habenula / pathology
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Male
  • Rats
  • Rats, Wistar
  • Signal Transduction / drug effects
  • Stress, Psychological / complications*
  • Stress, Psychological / genetics
  • Sucrose / pharmacology

Substances

  • Antidepressive Agents
  • Sucrose

Grants and funding

This study was supported by the Lundbeck Foundation (R77-A7085) – Lundbeckfonden.com, and Familien Hede Nielsens Fond, Augustinus Fonden, Direktør Jacob Madsen & Hustru Olga Madsens Fond, Søster og Verner Lipperts Fond, Gross. L.F. Foghts Fond, and Civilingeniør Frode V. Nyegaard og Hustrus Fond. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.