title: Negative regulation of microRNA-132 in expression of synaptic proteins in neuronal differentiation of embryonic neural stem cells.
abstract: MicroRNAs (miRs) play important roles in neuronal differentiation, maturation, and synaptic function in the central nervous system. They have also been suggested to be implicated in the pathogenesis of neurodegenerative and psychiatric diseases. Although miR-132 is one of the well-studied brain-specific miRs, which regulates synaptic structure and function in the postnatal brain, its function in the prenatal brain is still unclear. Here, we investigated miR-132 function during differentiation of rat embryonic neural stem cells (eNSCs). We found that miR-132 expression significantly increased during the fetal rat brain development and neural differentiation of eNSCs in vitro. Furthermore, miR-132 expression was increased during differentiation through MAPK/ERK1/2 pathway. Inhibition of ERK1/2 activation resulted in increased levels of synaptic proteins including PSD-95, GluR1 and synapsin I. Silencing of miR-132 also increased PSD-95 and GluR1. Considering that miR-132 increases synaptic proteins in differentiated cortical neurons, our result shows a novel function of miR-132 as a negative regulator for synaptic maturation in the neuronal differentiation of eNSCs.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Division of Laboratory Animals Resources, National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. Electronic address: numakawa.yyrmk@gmail.com.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Odaka
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan; Department of Biomedical Chemistry, Kwansei Gakuin University, Sanda, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.affiliation: Division of Laboratory Animals Resources, National Institute of Neuroscience, NCNP, Tokyo, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tamai
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000378:metabolism*; D015870:Gene Expression; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: C548821:MIRN132 microRNA, rat; D035683:MicroRNAs; D009419:Nerve Tissue Proteins
keywords: Differentiation; Embryonic neural stem cells; MAPK/ERK; MicroRNA; Synaptic proteins; miR-132