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Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) signi...

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Autores principales: Kim, Yoonhee, Zhang, Yinhua, Pang, Kaifang, Kang, Hyojin, Park, Heejoo, Lee, Yeunkum, Lee, Bokyoung, Lee, Heon-Jeong, Kim, Won-Ki, Geum, Dongho, Han, Kihoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society for Brain and Neural Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5195815/
https://www.ncbi.nlm.nih.gov/pubmed/28035180
http://dx.doi.org/10.5607/en.2016.25.6.296
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author Kim, Yoonhee
Zhang, Yinhua
Pang, Kaifang
Kang, Hyojin
Park, Heejoo
Lee, Yeunkum
Lee, Bokyoung
Lee, Heon-Jeong
Kim, Won-Ki
Geum, Dongho
Han, Kihoon
author_facet Kim, Yoonhee
Zhang, Yinhua
Pang, Kaifang
Kang, Hyojin
Park, Heejoo
Lee, Yeunkum
Lee, Bokyoung
Lee, Heon-Jeong
Kim, Won-Ki
Geum, Dongho
Han, Kihoon
author_sort Kim, Yoonhee
collection PubMed
description Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs.
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spelling pubmed-51958152016-12-29 Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses Kim, Yoonhee Zhang, Yinhua Pang, Kaifang Kang, Hyojin Park, Heejoo Lee, Yeunkum Lee, Bokyoung Lee, Heon-Jeong Kim, Won-Ki Geum, Dongho Han, Kihoon Exp Neurobiol Original Article Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs. The Korean Society for Brain and Neural Science 2016-12 2016-10-28 /pmc/articles/PMC5195815/ /pubmed/28035180 http://dx.doi.org/10.5607/en.2016.25.6.296 Text en Copyright © Experimental Neurobiology 2016. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Yoonhee
Zhang, Yinhua
Pang, Kaifang
Kang, Hyojin
Park, Heejoo
Lee, Yeunkum
Lee, Bokyoung
Lee, Heon-Jeong
Kim, Won-Ki
Geum, Dongho
Han, Kihoon
Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title_full Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title_fullStr Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title_full_unstemmed Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title_short Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses
title_sort bipolar disorder associated microrna, mir-1908-5p, regulates the expression of genes functioning in neuronal glutamatergic synapses
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5195815/
https://www.ncbi.nlm.nih.gov/pubmed/28035180
http://dx.doi.org/10.5607/en.2016.25.6.296
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