Innovations In Clinical Neuroscience

JAN-FEB 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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[ V O L U M E 1 4 , N U M B E R 1 – 2 , J A N U A R Y – F E B R U A R Y 2 0 1 7 ] Innovations in CLINICAL NEUROSCIENCE 53 ABSTRACT Neural-derived exosomes can be used as diagnostic markers to screen for various psychiatric conditions. These intravenously injected exosomes carry the potential to cross the blood brain barrier and deliver miRNA molecules specifically to neurons, microglia, and oligodendrocytes in the brain, resulting in specific gene knockdown. Here the authors review and discuss the current research on microRNA molecules and the therapeutic roles they may potentially play in treating depression, bipolar disorder, and schizophrenia. MicroRNAs AS BIOMARKERS FOR PSYCHIATRIC CONDITIONS The intrinsic ability of synapses to adapt to environmental pressures, physiologic changes, and escaping the restrictions imposed by the genome is termed neuronal or synaptic plasticity. 1 This includes molecular mechanisms and morphological changes, such as altered neurotransmitter release, altered receptor expression, and alteration of dendritic size, shape, and density. These adaptive changes, when dysregulated, may be involved in the pathogenesis of psychiatric disorders. In adult life, the effects of acute and chronic stress on neuronal plasticity is largely reversible, but early life stress induces persistent changes in neuronal plasticity that increase vulnerability to psychopathology, such as depression and posttraumatic stress disorder (PTSD), suggesting the involvement of epigenetic mechanisms. 2 Particularly in neurons, epigenetic control seems important, since neurons are challenged with converting complex environmental stimuli into high-order functions. There are several mechanisms in which the environment interacts with the genome, including deoxyribonucleic acid (DNA) methylation, histone modification, and microRNA regulation. A growing body of evidence demonstrates that micro- ribonucleic acid molecules (miRNAs) are key players in such epigenetic regulation. In this article, we review and discuss the current research on circulating microRNA molecules and the therapeutic roles they may potentially play in depression, bipolar disorder, and schizophrenia. WHAT ARE MicroRNAs? MicroRNAs are important regulators of post-transcriptional gene expression. They may up- or down-regulate the translation of messenger RNA (mRNA) or render it unstable. A single mRNA may be regulated by multiple miRNAs, and, conversely, some miRNAs have the potential to target hundreds of mRNAs. MiRNAs primarily act to negatively regulate gene expression; miRNA over- expression should lead to down- regulation of their gene targets resulting in a negative correlation. 3 However, reciprocal relationships between miRNAs levels and their targets are emerging. by ANOOP NARAHARI, MD; MARIYAH HUSSAIN, MD; and VENKATESH SREERAM, MD Drs. Narahari, Hussain, and Sreeram are from the University of Alabama, Department of Psychiatry and Behavioral sciences, Birmingham, Alabama. Innov Clin Neurosci. 2017;14(1–2):53–55 FUNDING: No funding was received for the preparation of this article. FINANCIAL DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article. ADDRESS CORRESPONDENCE TO: Dr. Anoop Narahari, Department of Psychiatry & Behavioral Neurobiology, University of Alabama at Birmingham, SC 1028, 1720 7th Avenue South, Birmingham, AL 35294-0017 Email address: narahari@uab.edu KEY WORDS: MicroRNA (miR/miRNA), messengerRNA (mRNA), neuronal plasticity, neurogenesis, hippocampus, depression, bipolar disorder, schizophrenia R E V I E W MicroRNAs as Biomarkers for Psychiatric Conditions: A Review of Current Research

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