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Implication of increased NRSF/REST binding activity in the mechanism of ethanol inhibition of neuronal differentiation

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Summary.

The neuron-restrictive silencer factor (NRSF), or repressor element-1 silencing transcription factor (REST), is a transcription factor that mediates negative regulation of neuronal genes. NRSF represses multiple neuronal target genes in non-neuronal and neuronal precursor cells to regulate the proper timing of neuronal gene expression during neurogenesis. In the present study, we investigated the effects of ethanol and MEK inhibitor U0126 on the DNA binding activity of NRSF in neural stem cells prepared from rat embryos. Both ethanol and U0126 enhanced NRSF binding activity measured by the method based on the principal of electrophoretic mobility shift assay (EMSA) and decreased neuronal differentiation in a concentration dependent manner. Western blot analysis revealed that ethanol suppressed phosphorylation of extracellular signal-regulated kinase (ERK) without affecting expression of total ERK. These results suggest that ethanol-induced potentiation of NRSF binding activity underlies the mechanism of ethanol inhibition of neuronal differentiation and decreased neurogenesis.

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References

  • Y Arsenijevic S Weiss (1998) ArticleTitleInsulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor. J Neurosci 18 2118–2128 Occurrence Handle1:CAS:528:DyaK1cXhs1ylsLo%3D Occurrence Handle9482798

    CAS  PubMed  Google Scholar 

  • F Barnabe-Heider FD Miller (2003) ArticleTitleEndogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathways. J Neurosci 23 5149–5160 Occurrence Handle1:CAS:528:DC%2BD3sXltlentLw%3D Occurrence Handle12832539

    CAS  PubMed  Google Scholar 

  • L Chang M Karin (2001) ArticleTitleMammalian MAP kinase signaling cascades. Nature 410 37–40 Occurrence Handle1:CAS:528:DC%2BD3MXhvVSgs7k%3D Occurrence Handle11242034

    CAS  PubMed  Google Scholar 

  • MY Chang H Son YS Lee SH Lee (2003) ArticleTitleNeurons and astrocytes secrete factors that cause stem cells to differentiate into neurons and astrocytes, respectively. Mol Cell Neurosci 23 414–426 Occurrence Handle10.1016/S1044-7431(03)00068-X Occurrence Handle1:CAS:528:DC%2BD3sXkvFGntrw%3D Occurrence Handle12837625

    Article  CAS  PubMed  Google Scholar 

  • ZF Chen AJ Paquette DJ Anderson (1998) ArticleTitleNRSF/REST is required in vivo for repression of multiple neuronal target genes during embryogenesis. Nat Genet 20 136–142 Occurrence Handle10.1038/2431 Occurrence Handle1:CAS:528:DyaK1cXms1aku7o%3D Occurrence Handle9771705

    Article  CAS  PubMed  Google Scholar 

  • JA Chong J Tapia-Ramirez S Kim JJ Toledo-Aral Y Zheng MC Boutros YM Altshuller MA Frohman SD Kraner G Mandel (1995) ArticleTitleREST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80 949–957 Occurrence Handle10.1016/0092-8674(95)90298-8 Occurrence Handle1:CAS:528:DyaK2MXkslOmur0%3D Occurrence Handle7697725

    Article  CAS  PubMed  Google Scholar 

  • SK Clarren DW Smith (1978) ArticleTitleThe fetal alcohol syndrome. N Engl J Med 298 1063–1067 Occurrence Handle1:STN:280:CSeC2Mnis1M%3D Occurrence Handle347295

    CAS  PubMed  Google Scholar 

  • FT Crews MW Miller W Ma K Nixon WM Zawada S Zakhari (2003) ArticleTitleNeural stem cells and alcohol. Alcohol Clin Exp Res 27 324–335 Occurrence Handle1:STN:280:DC%2BD3s%2FptFOjsw%3D%3D Occurrence Handle12605082

    CAS  PubMed  Google Scholar 

  • RS Duman (2004) ArticleTitleRole of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med 5 11–25 Occurrence Handle10.1385/NMM:5:1:011 Occurrence Handle1:CAS:528:DC%2BD2cXivVCiuro%3D

    Article  CAS  Google Scholar 

  • N Durany T Michel R Zochling KW Boissl FF Cruz-Sanchez P Riederer J Thome (2001) ArticleTitleBrain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 52 79–86 Occurrence Handle10.1016/S0920-9964(00)00084-0 Occurrence Handle1:STN:280:DC%2BD3MrkvFClsw%3D%3D Occurrence Handle11595394

    Article  CAS  PubMed  Google Scholar 

  • AJ Eisch CD Mandyam (2004) ArticleTitleDrug dependence and addiction. II. Adult neurogenesis and drug abuse. Am J Psychiatry 161 426 Occurrence Handle10.1176/appi.ajp.161.3.426 Occurrence Handle14992964

    Article  PubMed  Google Scholar 

  • PS Eriksson E Perfilieva T Bjork-Eriksson AM Alborn C Nordborg DA Peterson FH Gage (1998) ArticleTitleNeurogenesis in the adult human hippocampus. Nat Med 4 1313–1317 Occurrence Handle10.1038/3305 Occurrence Handle1:CAS:528:DyaK1cXntlaktb4%3D Occurrence Handle9809557

    Article  CAS  PubMed  Google Scholar 

  • C Harper I Matsumoto (2005) ArticleTitleEthanol and brain damage. Curr Opin Pharmacol 5 73–78 Occurrence Handle1:CAS:528:DC%2BD2MXms1Clsg%3D%3D Occurrence Handle15661629

    CAS  PubMed  Google Scholar 

  • DG Herrera AG Yague S Johnsen-Soriano F Bosch-Morell L Collado-Morente M Muriach FJ Romero JM Garcia-Verdugo (2003) ArticleTitleSelective impairment of hippocampal neurogenesis by chronic alcoholism: protective effects of an antioxidant. Proc Natl Acad Sci USA 100 7919–7924 Occurrence Handle10.1073/pnas.1230907100 Occurrence Handle1:CAS:528:DC%2BD3sXlt1Wqtrk%3D Occurrence Handle12792022

    Article  CAS  PubMed  Google Scholar 

  • JS Jacobs MW Miller (2001) ArticleTitleProliferation and death of cultured fetal neocortical neurons: effects of ethanol on the dynamics of cell growth. J Neurocytol 30 391–401 Occurrence Handle1:CAS:528:DC%2BD38XksFGgsb8%3D Occurrence Handle11951050

    CAS  PubMed  Google Scholar 

  • S Kao RK Jaiswal W Kolch GE Landreth (2001) ArticleTitleIdentification of the mechanisms regulating the differential activation of the MAPK cascade by epidermal growth factor and nerve growth factor in PC12 cells. J Biol Chem 276 18169–18177 Occurrence Handle1:CAS:528:DC%2BD3MXktFWmsLk%3D Occurrence Handle11278445

    CAS  PubMed  Google Scholar 

  • F Karege G Perret G Bondolfi M Schwald G Bertschy JM Aubry (2002) ArticleTitleDecreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109 143–148 Occurrence Handle10.1016/S0165-1781(02)00005-7 Occurrence Handle1:CAS:528:DC%2BD38Xitlaqt70%3D Occurrence Handle11927139

    Article  CAS  PubMed  Google Scholar 

  • SD Kraner JA Chong HJ Tsay G Mandel (1992) ArticleTitleSilencing the type II sodium channel gene: a model for neural-specific gene regulation. Neuron 9 37–44 Occurrence Handle10.1016/0896-6273(92)90218-3 Occurrence Handle1:CAS:528:DyaK3sXitVKksbo%3D Occurrence Handle1321645

    Article  CAS  PubMed  Google Scholar 

  • B Lindblad R Olsson (1976) ArticleTitleUnusually high levels of blood alcohol? JAMA 236 1600–1602 Occurrence Handle10.1001/jama.236.14.1600 Occurrence Handle1:STN:280:CSmB28rjsVw%3D Occurrence Handle989133

    Article  CAS  PubMed  Google Scholar 

  • RA Maue SD Krane RH Goodman G Mandel (1990) ArticleTitleNeuron-specific expression of the rat brain type II sodium channel gene is directed by upstream regulatory elements. Neuron 4 223–231 Occurrence Handle10.1016/0896-6273(90)90097-Y Occurrence Handle1:CAS:528:DyaK3cXltFShtLk%3D Occurrence Handle2155009

    Article  CAS  PubMed  Google Scholar 

  • N Mori C Schoenherr DJ Vandenbergh DJ Anderson (1992) ArticleTitleA common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells. Neuron 9 45–54 Occurrence Handle10.1016/0896-6273(92)90219-4 Occurrence Handle1:CAS:528:DyaK3sXhtFyjsbo%3D Occurrence Handle1321646

    Article  CAS  PubMed  Google Scholar 

  • N Mori R Stein O Sigmund DJ Anderson (1990) ArticleTitleA cell type-preferred silencer element that controls the neural-specific expression of the SCG10 gene. Neuron 4 583–594 Occurrence Handle10.1016/0896-6273(90)90116-W Occurrence Handle1:CAS:528:DyaK3cXltFShtLc%3D Occurrence Handle2322462

    Article  CAS  PubMed  Google Scholar 

  • S O’Neill KF Tipton JS Prichard A Quinlan (1984) ArticleTitleSurvival after high blood alcohol levels. Association with first-order elimination kinetics. Arch Intern Med 144 641–642 Occurrence Handle1:STN:280:BiuC2MzgsFE%3D Occurrence Handle6703836

    CAS  PubMed  Google Scholar 

  • BA Reynolds S Weiss (1992) ArticleTitleGeneration of neurons and astrocytes from isolated cells of the mammalian central nervous system. Science 255 1707–1710 Occurrence Handle1:STN:280:By2B3crjsFU%3D Occurrence Handle1553558

    CAS  PubMed  Google Scholar 

  • CJ Schoenherr DJ Anderson (1995a) ArticleTitleSilencing is golden: negative regulation in the control of neuronal gene transcription. Curr Opin Neurobiol 5 566–571 Occurrence Handle10.1016/0959-4388(95)80060-3 Occurrence Handle1:CAS:528:DyaK2MXps1ynt7g%3D

    Article  CAS  Google Scholar 

  • CJ Schoenherr DJ Anderson (1995b) ArticleTitleThe neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 267 1360–1363 Occurrence Handle1:CAS:528:DyaK2MXktF2it7w%3D

    CAS  Google Scholar 

  • P Simpson (1995) ArticleTitlePositive and negative regulators of neural fate. Neuron 15 739–742 Occurrence Handle10.1016/0896-6273(95)90163-9 Occurrence Handle1:CAS:528:DyaK2MXptV2gsrg%3D Occurrence Handle7576621

    Article  CAS  PubMed  Google Scholar 

  • EV Sullivan L Marsh (2003) ArticleTitleHippocampal volume deficits in alcoholic Korsakoff’s syndrome. Neurology 61 1716–1719 Occurrence Handle14694035

    PubMed  Google Scholar 

  • VW Swayze Suffix2nd VP Johnson JW Hanson J Piven Y Sato JN Giedd D Mosnik NC Andreasen (1997) ArticleTitleMagnetic resonance imaging of brain anomalies in fetal alcohol syndrome. Pediatrics 99 232–240 Occurrence Handle10.1542/peds.99.2.232 Occurrence Handle9024452

    Article  PubMed  Google Scholar 

  • J Sweatt (2001) ArticleTitleThe neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem 76 1–10 Occurrence Handle10.1046/j.1471-4159.2001.00054.x Occurrence Handle1:CAS:528:DC%2BD3MXhtVGls7w%3D Occurrence Handle11145972

    Article  CAS  PubMed  Google Scholar 

  • J Tapia-Ramirez BJ Eggen MJ Peral-Rubio JJ Toledo-Aral G Mandel (1997) ArticleTitleA single zinc finger motif in the silencing factor REST represses the neural-specific type II sodium channel promoter. Proc Natl Acad Sci USA 94 1177–1182 Occurrence Handle10.1073/pnas.94.4.1177 Occurrence Handle1:CAS:528:DyaK2sXhtlGgtLg%3D Occurrence Handle9037026

    Article  CAS  PubMed  Google Scholar 

  • M Tateno W Ukai H Ozawa M Yamamoto S Toki H Ikeda T Saito (2004) ArticleTitleEthanol inhibition of neural stem cell differentiation is reduced by neurotrophic factors. Alcohol Clin Exp Res 28 134S–138S Occurrence Handle1:CAS:528:DC%2BD2cXmsl2gsL4%3D Occurrence Handle15318100

    CAS  PubMed  Google Scholar 

  • G Thiel M Lietz M Cramer (1998) ArticleTitleBiological activity and modular structure of RE-1-silencing transcription factor (REST), a repressor of neuronal genes. J Biol Chem 273 26891–26899 Occurrence Handle10.1074/jbc.273.41.26891 Occurrence Handle1:CAS:528:DyaK1cXmslais7w%3D Occurrence Handle9756936

    Article  CAS  PubMed  Google Scholar 

  • K Toyooka K Asama Y Watanabe T Muratake M Takahashi T Someya H Nawa (2002) ArticleTitleDecreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 110 249–257 Occurrence Handle10.1016/S0165-1781(02)00127-0 Occurrence Handle1:CAS:528:DC%2BD38XlsVKrsbo%3D Occurrence Handle12127475

    Article  CAS  PubMed  Google Scholar 

  • W Ukai H Ozawa M Tateno E Hashimoto T Saito (2004) ArticleTitleNeurotoxic potential of haloperidol in comparison with risperidone: implication of Akt-mediated signal changes by haloperidol. J Neural Transm 111 667–681 Occurrence Handle10.1007/s00702-004-0109-z Occurrence Handle1:CAS:528:DC%2BD2cXksVensb0%3D Occurrence Handle15168214

    Article  CAS  PubMed  Google Scholar 

  • T Urso JS Gavaler DH Van Thiel (1981) ArticleTitleBlood ethanol levels in sober alcohol users seen in an emergency room. Life Sci 28 1053–1056 Occurrence Handle10.1016/0024-3205(81)90752-9 Occurrence Handle1:STN:280:Bi6C2s3gtlI%3D Occurrence Handle7219065

    Article  CAS  PubMed  Google Scholar 

  • DW Walker DE Barnes SF Zornetzer BE Hunter P Kubanis (1980) ArticleTitleNeuronal loss in hippocampus induced by prolonged ethanol consumption in rats. Science 209 711–713 Occurrence Handle1:CAS:528:DyaL3cXlt1KrtLw%3D Occurrence Handle7394532

    CAS  PubMed  Google Scholar 

  • M Yamada K Tanabe K Wada K Shimoke Y Ishikawa T Ikeuchi S Koizumi H Hatanaka (2001) ArticleTitleDifferences in survival-promoting effects and intracellular signaling properties of BDNF and IGF-1 in cultured cerebral cortical neurons. J Neurochem 78 940–951 Occurrence Handle10.1046/j.1471-4159.2001.00497.x Occurrence Handle1:CAS:528:DC%2BD3MXms12kurk%3D Occurrence Handle11553668

    Article  CAS  PubMed  Google Scholar 

  • RD York H Yao T Dillon CL Ellig SP Eckert EW McCleskey PJ Stork (1998) ArticleTitleRap1 mediates sustained MAP kinase activation induced by nerve growth factor. Nature 392 622–626 Occurrence Handle1:CAS:528:DyaK1cXis1Wjtrs%3D Occurrence Handle9560161

    CAS  PubMed  Google Scholar 

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  1. Department of Neuropsychiatry, Sapporo Medical University, School of Medicine, Sapporo, Japan

    M. Tateno, W. Ukai, E. Hashimoto, H. Ikeda & T. Saito

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  1. M. Tateno
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  2. W. Ukai
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  3. E. Hashimoto
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  4. H. Ikeda
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  5. T. Saito
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Tateno, M., Ukai, W., Hashimoto, E. et al. Implication of increased NRSF/REST binding activity in the mechanism of ethanol inhibition of neuronal differentiation. J Neural Transm 113, 283–293 (2006). https://doi.org/10.1007/s00702-005-0320-6

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  • DOI: https://doi.org/10.1007/s00702-005-0320-6

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