Bipolar disorder associated microRNA, miR- 1908-5p, regulates the expression of genes functioning in neuronal glutamatergic synapses

Yoonhee Kim, Yinhua Zhang, Kaifang Pang, Hyojin Kang, Heejoo Park, Yeunkum Lee, Bokyoung Lee, Heon Jeong Lee, Won Ki Kim, Dongho Geum, Kihoon Han

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)296-306
Number of pages11
JournalExperimental Neurobiology
Volume25
Issue number6
DOIs
Publication statusPublished - 2016

Keywords

  • Bipolar disorder
  • Glutamatergic synapse
  • MiR-1908-5p
  • MicroRNA

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Bipolar disorder associated microRNA, miR- 1908-5p, regulates the expression of genes functioning in neuronal glutamatergic synapses'. Together they form a unique fingerprint.

  • Cite this