MicroRNAs and epigenetic regulation of the stress response

Most psychiatric disorders display a strong genetic component, but heritability by itself can only partially explain an individual’s risk to develop a mental disorder. Environmental factors — mainly exposure to psychological or physiological stressors — have been associated with psychiatric morbidity. A complex interaction between genetic predisposition and environmental factors is suggested to be at the root of mental illness. Environmental factors can, through epigenetic mechanisms, induce changes in genes expression levels that might mediate the onset of a disease without altering the DNA sequence. These mechanisms include histone modification, DNA methylation, and post-transcriptional regulation by non-coding RNAs such as microRNAs (miRNAs), which are the main focus of current projects in the lab.
We go far toward characterizing the mechanisms by which specific miRs are mediating behavioral functions under normal and challenged conditions. We employ integrated molecular, biochemical, physiological and behavioral methods, focusing on the use of mice models as an in vivo tool, in order to study the physiological role of specific stress-linked miRNAs in regulating behavioral responses under normal and challenged conditions. Genetic manipulation of specific miRNA molecules, in the whole animal context, permit us to examine their specific role in modulating behavioral functions. Understanding the regulatory role of specific miRNAs in selected stress-related central locations will provide important insights into the brain mechanisms by which stress is involved in mediating stress-linked disorders.

Relevant Publications

Volk N, Pape J.C, Engel M, Zannas A.S, Cattane N, Cattaneo A, Binder E.B, Chen A (2016). Amygdalar Microrna-15a is Essential For Coping With Chronic Stress.  Cell Reports. 17: :1882–91.
Elliott E, Manashirov S, Zwang R, Gil S, Tsoory M, Shemesh Y, Chen A (2016). Dnmt3a in the Medial Prefrontal Cortex Regulates Anxiety-Like Behavior in Adult Mice.  Journal of Neuroscience. 36(3): :730-740.
Vaisvaser S, Modai S, Farberov L, Lin T, Sharon H, Gilam A, Volk N, Admon R, Edry L, Fruchter E, Wald I, Bar-Haim Y, Tarrasch R, Chen A, Shomron N, Hendler T (2016). Neuro-Epigenetic Indications of Acute Stress Response in Humans: the Case of Microrna-29c..  PLoS ONE. 11(1). .
Issler O, Chen A (2015). Determining the Role of Micrornas in Psychiatric Disorders.  Nature Reviews Neuroscience.. 16: :201–212 .
Volk N, Paul Ed, Haramati S, Eitan C, Fields Bkk, Zwang R, Gil S, Lowry Ca, Chen A, (2014). Microrna-19b Associates With Ago2 in the Amygdala Following Chronic Stress and Regulates the Adrenergic Receptor Beta 1.  Journal of Neuroscience. 34: (45):15070-15082.
Issler O, Haramati S, Paul Ed, Maeno H, Navon I, Zwang R, Gil S, Mayberg Hs, Dunlop Bw, Menke A, Awatramani R, Binder Eb, Deneris Es, Lowry Ca, Chen A, (2014). Microrna 135 is Essential For Chronic Stress Resiliency, Antidepressant Efficacy, and Intact Serotonergic Activity.  Neuron. 83: (2):344-360.
Haramati S, Navon I, Issler O, Ezra-Nevo G, Gil S, Zwang R, Hornstein E, Chen A, (2011). Microrna as Repressors of Stress-Induced Anxiety: the Case of Amygdalar Mir-34.  Journal of Neuroscience. 31: (40):14191-14203.
Elliott E, Ezra-Nevo G, Regev L, Neufeld-Cohen A, Chen A, (2010). Resilience to Social Stress Coincides With Functional DNA Methylation of the Crf Gene in Adult Mice.  Nature Neuroscience. 13: (11):1351-1353.