miRNA regulation of social and anxiety-related behaviour
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Cellular and Molecular Life Sciences
REVIEW
miRNA regulation of social and anxiety‑related behaviour Ramanathan Narayanan1 · Gerhard Schratt1 Received: 19 November 2019 / Revised: 31 March 2020 / Accepted: 27 April 2020 © Springer Nature Switzerland AG 2020
Abstract Neuropsychiatric disorders, including autism spectrum disorders (ASD) and anxiety disorders are characterized by a complex range of symptoms, including social behaviour and cognitive deficits, depression and repetitive behaviours. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their aetiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as a new gene regulatory layer in the pathophysiology of mental illness. These small RNAs can bind to the 3′-UTR of mRNA thereby negatively regulating gene expression at the post-transcriptional level. Their ability to regulate hundreds of target mRNAs simultaneously predestines them to control the activity of entire cellular pathways, with obvious implications for the regulation of complex processes such as animal behaviour. There is growing evidence to suggest that numerous miRNAs are dysregulated in pathophysiology of neuropsychiatric disorders, and there is strong genetic support for the association of miRNA genes and their targets with several of these conditions. This review attempts to cover the most relevant microRNAs for which an important contribution to the control of social and anxiety-related behaviour has been demonstrated by functional studies in animal models. In addition, it provides an overview of recent expression profiling and genetic association studies in human patient-derived samples in an attempt to highlight the most promising candidates for biomarker discovery and therapeutic intervention. Keywords miRNA · Sociability · Anxiety · Behaviour Abbreviations AAV Adeno associated virus AChE Acetyl cholinesterase AGO Argonaute AMPAR α-Amino-3-hydroxy-5-methyl-4isoxazolepropionic acid receptor AS Acute stress ASD Autism spectrum disorder BChE Butyrylcholinesterase BD Bipolar disorder BDNF Brain-derived neurotrophic factor BLA Basolateral amygdala CA1 Cornu Ammonis area 1 Cas9 CRISPR associated protein 9 cAMP Cyclic adenosine triphosphate CCKBR Cholecystokinin B receptor * Gerhard Schratt [email protected] 1
Lab of Systems Neuroscience, Department of Health Science and Technology, Institute for Neuroscience, Swiss Federal Institute of Technology ETH, Zurich, Switzerland
CeA Central amygdala cGMP Cyclic guanine triphosphate CHMP2B Charged multivesicular body protein 2b circRNA Circular RNA CNR1 Cannabinoid receptor type 1 CNV Copy number variation CRF Corticotrophin releasing factor CRFR1 Corticotrophin releasing factor receptor 1 CRHR1 Corticotrophin releasing hormone receptor 1 CRISPR Clustered regularly interspaced short palindromic repeats CRS Chronic restraint stress DG D
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