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Neuron. 2014 Jul 16;83(2):344-360. doi: 10.1016/j.neuron.2014.05.042. Epub 2014 Jun 19.

MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity.

Author information

1
The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel; Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, 80804 Munich, Germany.
2
The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.
3
Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO 80309, USA.
4
Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
5
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
6
Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany.
7
Department of Neurology and Center for Genetic Medicine, Northwestern University Feinberg Medical School, Chicago, IL 60611, USA.
8
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany.
9
The Ruhman Family Laboratory for Research on the Neurobiology of Stress, Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel; Department of Stress Neurobiology and Neurogenetics, Max-Planck Institute of Psychiatry, 80804 Munich, Germany. Electronic address: alon.chen@weizmann.ac.il.

Abstract

The link between dysregulated serotonergic activity and depression and anxiety disorders is well established, yet the molecular mechanisms underlying these psychopathologies are not fully understood. Here, we explore the role of microRNAs in regulating serotonergic (5HT) neuron activity. To this end, we determined the specific microRNA "fingerprint" of 5HT neurons and identified a strong microRNA-target interaction between microRNA 135 (miR135), and both serotonin transporter and serotonin receptor-1a transcripts. Intriguingly, miR135a levels were upregulated after administration of antidepressants. Genetically modified mouse models, expressing higher or lower levels of miR135, demonstrated major alterations in anxiety- and depression-like behaviors, 5HT levels, and behavioral response to antidepressant treatment. Finally, miR135a levels in blood and brain of depressed human patients were significantly lower. The current results suggest a potential role for miR135 as an endogenous antidepressant and provide a venue for potential treatment and insights into the onset, susceptibility, and heterogeneity of stress-related psychopathologies.

PMID:
24952960
DOI:
10.1016/j.neuron.2014.05.042
[Indexed for MEDLINE]
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