Big effects of small RNAs: a review of microRNAs in anxiety.

Stefanie Malan-Müller,Sîan Megan Joanna Hemmings,Soraya Seedat

doi:10.1007/s12035-012-8374-6

Stefanie Malan-Müller, Sîan Megan Joanna Hemmings + Show 1 more

Open Access

https://doi.org/10.1007/s12035-012-8374-6

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Journal: Molecular Neurobiology	Publication Date: Nov 13, 2012
Citations: 77	License type: cc-by

Affiliation: Stellenbosch University

Abstract

Epigenetic and regulatory elements provide an additional layer of complexity to the heterogeneity of anxiety disorders. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that have recently drawn interest as epigenetic modulators of gene expression in psychiatric disorders. miRNAs elicit their effects by binding to target messenger RNAs (mRNAs) and hindering translation or accelerating degradation. Considering their role in neuronal differentiation and synaptic plasticity, miRNAs have opened up new investigative avenues in the aetiology and treatment of anxiety disorders. In this review, we provide a thorough analysis of miRNAs, their targets and their functions in the central nervous system (CNS), focusing on their role in anxiety disorders. The involvement of miRNAs in CNS functions (such as neurogenesis, neurite outgrowth, synaptogenesis and synaptic and neural plasticity) and their intricate regulatory role under stressful conditions strongly support their importance in the aetiology of anxiety disorders. Furthermore, miRNAs could provide new avenues for the development of therapeutic targets in anxiety disorders.

Highlights

Anxiety disorders are a heterogeneous group of disorders that include acute stress disorder, agoraphobia, generalised anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder (PD), phobias and posttraumatic stress disorder (PTSD) [1]
Results indicated an increased level of expression of genes and miRNAs possibly regulated by repressor element-1 silencing transcription factor 4 (REST4), such as glutamate receptor subunit (Glur2), calcium/calmodulin-dependent protein kinase II (CamKIIα) and adenylate cyclase 5 (Adcy5) as well as precursors for mir132, -124 and -212. These results suggest a role for an REST4-mediated gene network and specific miRNAs acting in the medial prefrontal cortex (mPFC)
MiRNAs are of particular importance in anxiety disorders for a number of reasons

Summary

Introduction

Anxiety disorders are a heterogeneous group of disorders that include acute stress disorder, agoraphobia (with or without a history of panic disorder), generalised anxiety disorder (GAD), obsessive-compulsive disorder (OCD), panic disorder (PD) (with or without agoraphobia), phobias (including social anxiety disorder) and posttraumatic stress disorder (PTSD) [1] These disorders cause significant distress and functional impairments, and collectively have an estimated lifetime prevalence of up to 25 % [2]. Functional magnetic resonance imaging (fMRI) studies have revealed increased baseline activity in the parahippocampal gyrus and the cingulate cortex [5] and increased brain activity in the amygdala, parahippocampal gyrus and frontal cortex in response to anxietyinducing stimuli [6] These findings suggest an important role for the forebrain, as a site of increased excitatory neurotransmission, in the anxiety disorders

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