title: 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.
abstract: 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.
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors: Katrine
authors: K
authors: Svenningsen
authors: Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
authors: Morten T
authors: MT
authors: Venø
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors: Kim
authors: K
authors: Henningsen
authors: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Anne S
authors: AS
authors: Mallien
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors: Line
authors: L
authors: Jensen
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors: Trine
authors: T
authors: Christensen
authors: Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
authors: Jørgen
authors: J
authors: Kjems
authors: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors: Barbara
authors: B
authors: Vollmayr
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark.
authors: Ove
authors: O
authors: Wiborg
mesh_terms: D000818:Animals; D001835:Body Weight; D004597:Electroshock; D020869:Gene Expression Profiling; D005819:Genetic Markers; D019262:Habenula / Q000502:physiology*; D006380:Helplessness, Learned; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D017207:Rats, Sprague-Dawley
chemical_list: D005819:Genetic Markers; D035683:MicroRNAs