MicroRNA dysregulation in neuropsychiatric disorders and cognitive dysfunction

Abstract

MicroRNAs (miRNA), a class of non-coding RNAs, are emerging as important modulators of neuronal development, structure and function. A connection has been established between abnormalities in miRNA expression and miRNA-mediated gene regulation and psychiatric and neurodevelopmental disorders as well as cognitive dysfunction. Establishment of this connection has been driven by progress in elucidating the genetic etiology of these phenotypes and has provided a context to interpret additional supporting evidence accumulating from parallel expression profiling studies in brains and peripheral blood of patients. Here we review relevant evidence that supports this connection and explore possible mechanisms that underlie the contribution of individual miRNAs and miRNA-related pathways to the pathogenesis and pathophysiology of these complex clinical phenotypes. The existing evidence provides useful hypotheses for further investigation as well as important clues for identifying novel therapeutic targets.

The Pattern of Cortical Dysfunction in a Mouse Model of a Schizophrenia-Related Microdeletion

“…Finally, our findings are in line with accumulating evidence that miRNAs play an important role in the pathogenesis and pathophysiology of psychiatric disorders and cognitive dysfunction Miller et al, 2012;Xu et al, , 2012bXu et al, , 2013, as well as with additional supporting evidence accumulating from parallel expression profiling studies in brains and peripheral blood of patients (Perkins et al, 2007;Beveridge et al, 2008;Moreau et al, 2011;Miller et al, 2012). Importantly, we recently provided evidence that rare de novo deleterious mutations in genes showing a prenatal expression bias and miRNA regulation are enriched in individuals with SCZ, especially those with prominent early prepsychotic, deviant behaviors (Gilman et al, 2012;Xu et al, 2012a).…”

Genes with de novo mutations are shared by four neuropsychiatric disorders discovered from NPdenovo database

“…Most previous studies have focused on the biological function of genes in coding regions. Given by the facts that mutations in non-coding regulatory regions are also involved in etiology of human diseases 63, 64 , regulation in non-coding regions is particularly important for brain development 44, 65 and neuropsychiatric disorders 66, 67 , we strongly propose that DNMs located in transcription factor and microRNA target sites may participate in the pathology of these four disorders.…”

Autism, Development and Neural Plasticity

“…The recently discovered microRNAs (miRNAs) are a class of endogenous small noncoding RNAs able to regulate translation or transcription of specific mRNAs (Liu and Kohane 2009;Xu et al 2012). They can repress translation of hundreds of genes and target a multitude of cellular mechanisms (Costa-Mattioli et al 2009;Costa et al 2012).…”

“…The miR-132 also regulates the immune response and is recognized to be induced by endotoxines (Im and Kenny 2012;Hansen et al 2013) and to be affected by cytomegalovirus infection, contributing to autism pathogenesis (Onore et al 2012b, a). Also, it is known that miR-132 has an effect on the synaptic structure, which is modulated by the Fragile X protein (FMRP), a product of the Fmr gene responsible for fragile X mental retardation, and a reduced level of miR-132 is found in Rett syndrome (D'Hulst and Kooy 2009; Xu et al 2012;Olde Loohuis et al 2012).…”