Molecular Profiling of the Lateral Habenula in a Rat Model of Depression

Trine Christensen,Line Jensen,Ove Wiborg,Elena V Bouzinova,Veronique Sgambato-Faure

doi:10.1371/journal.pone.0080666

Abstract

ObjectiveThis study systematically investigated the effect of chronic mild stress and response to antidepressant treatment in the lateral habenula at the whole genome level.MethodsRat 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.ResultsIn 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.ConclusionThe 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.

Highlights

Depression is a major cause of disability affecting about 350 million people worldwide
In the present study we investigated global transcriptomic profiles of chronic mild stress (CMS) phenotypes to search for biomarkers/molecular mechanisms underlying vulnerability to depression and the long-term action of antidepressant treatment
The results of the present study indicate that stress-induced anhedonia and antidepressant treatment primarily associated with changes in intracellular signaling mechanisms in the lateral habenula (LHb)

Summary

Introduction

Depression is a major cause of disability affecting about 350 million people worldwide. Little is known about the underlying pathology of the disease. The complexity of the disease is massive involving several neurological mechanisms and affecting numerous regions of the brain. The therapeutic intervention of depression-associated symptoms has evolved rapidly over the past two decades. Currently available antidepressants have significant limitations, including slow onset of action and low rates of response including treatment refraction. Despite substantial advances in understanding depression symptomatology, as well as the antidepressant machinery, the underlying molecular mechanisms still remain unclear [1]

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Results

Conclusion