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(WangHWangJNingC Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I:C. Sci Rep 2017; 7(1): 9709.28852164)
WangHWangJNingC Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I:C. Sci Rep 2017; 7(1): 9709.28852164WangHWangJNingC Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I:C. Sci Rep 2017; 7(1): 9709.28852164, WangHWangJNingC Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I:C. Sci Rep 2017; 7(1): 9709.28852164
(KimSKaangBK. Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 2017; 49(1): e281.)
KimSKaangBK. Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 2017; 49(1): e281.KimSKaangBK. Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 2017; 49(1): e281., KimSKaangBK. Epigenetic regulation and chromatin remodeling in learning and memory. Exp Mol Med 2017; 49(1): e281.
(PennerMRRothTLChawlaMK Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011; 32(12): 2198–2210.20189687)
PennerMRRothTLChawlaMK Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011; 32(12): 2198–2210.20189687PennerMRRothTLChawlaMK Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011; 32(12): 2198–2210.20189687, PennerMRRothTLChawlaMK Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011; 32(12): 2198–2210.20189687
(ZhaoZLanMLiJ The proinflammatory cytokine TNFα induces DNA demethylation-dependent and-independent activation of interleukin-32 expression. J Biol Chem 2019; 294: 6785–6795.30824537)
ZhaoZLanMLiJ The proinflammatory cytokine TNFα induces DNA demethylation-dependent and-independent activation of interleukin-32 expression. J Biol Chem 2019; 294: 6785–6795.30824537ZhaoZLanMLiJ The proinflammatory cytokine TNFα induces DNA demethylation-dependent and-independent activation of interleukin-32 expression. J Biol Chem 2019; 294: 6785–6795.30824537, ZhaoZLanMLiJ The proinflammatory cytokine TNFα induces DNA demethylation-dependent and-independent activation of interleukin-32 expression. J Biol Chem 2019; 294: 6785–6795.30824537
Haifei Wang, Jiying Wang, C. Ning, Xianrui Zheng, Jinlian Fu, Aiguo Wang, Qin Zhang, Jianfeng Liu (2017)
Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I:CScientific Reports, 7
(RothTLSweattJD. Regulation of chromatin structure in memory formation. Curr Opin Neurobiol 2009; 19: 336–342.19539459)
RothTLSweattJD. Regulation of chromatin structure in memory formation. Curr Opin Neurobiol 2009; 19: 336–342.19539459RothTLSweattJD. Regulation of chromatin structure in memory formation. Curr Opin Neurobiol 2009; 19: 336–342.19539459, RothTLSweattJD. Regulation of chromatin structure in memory formation. Curr Opin Neurobiol 2009; 19: 336–342.19539459
Wai-Yu Li, Yi-Chun Chang, L. Lee, Li-Jen Lee (2014)
Prenatal Infection Affects the Neuronal Architecture and Cognitive Function in Adult MiceDevelopmental Neuroscience, 36
(KundakovicMJaricI. The epigenetic link between prenatal adverse environments and neurodevelopmental disorders. Genes (Basel Stiles) 2017; 8(3): pii: E104.)
KundakovicMJaricI. The epigenetic link between prenatal adverse environments and neurodevelopmental disorders. Genes (Basel Stiles) 2017; 8(3): pii: E104.KundakovicMJaricI. The epigenetic link between prenatal adverse environments and neurodevelopmental disorders. Genes (Basel Stiles) 2017; 8(3): pii: E104., KundakovicMJaricI. The epigenetic link between prenatal adverse environments and neurodevelopmental disorders. Genes (Basel Stiles) 2017; 8(3): pii: E104.
Sylvie Janssens, M. Schotsaert, Rahul Karnik, V. Balasubramaniam, M. Déjosez, A. Meissner, A. García-Sastre, T. Zwaka (2018)
Zika Virus Alters DNA Methylation of Neural Genes in an Organoid Model of the Developing Human BrainmSystems, 3
(DulacC. Brain function and chromatin plasticity. Nature 2010; 465: 728–735.20535202)
DulacC. Brain function and chromatin plasticity. Nature 2010; 465: 728–735.20535202DulacC. Brain function and chromatin plasticity. Nature 2010; 465: 728–735.20535202, DulacC. Brain function and chromatin plasticity. Nature 2010; 465: 728–735.20535202
Zuodong Zhao, Mengying Lan, Jingjing Li, Q. Dong, Xiang Li, Baodong Liu, Gang Li, Hailin Wang, Zhuqiang Zhang, B. Zhu (2019)
The proinflammatory cytokine TNFα induces DNA demethylation–dependent and –independent activation of interleukin-32 expressionThe Journal of Biological Chemistry, 294
(CarterSDMifsudKRReulJM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci 2015; 16: 156.)
CarterSDMifsudKRReulJM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci 2015; 16: 156.CarterSDMifsudKRReulJM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci 2015; 16: 156., CarterSDMifsudKRReulJM. Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci 2015; 16: 156.
(BradfordMM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.942051)
BradfordMM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.942051BradfordMM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.942051, BradfordMM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.942051
P. Silva, C. Gigek, M. Leal, P. Bertolucci, R. Labio, S. Payão, Marília Smith (2008)
Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer's disease.Journal of Alzheimer's disease : JAD, 13 2
M. Kundakovic, I. Jarić (2017)
The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental DisordersGenes, 8
A. Fischer, F. Sananbenesi, Xinyu Wang, Matthew Dobbin, L. Tsai (2007)
Recovery of learning and memory is associated with chromatin remodellingNature, 447
(FieldRCampionSWarrenC Systemic challenge with the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta and IL1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 2010; 24(6): 996–1007.20399848)
FieldRCampionSWarrenC Systemic challenge with the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta and IL1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 2010; 24(6): 996–1007.20399848FieldRCampionSWarrenC Systemic challenge with the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta and IL1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 2010; 24(6): 996–1007.20399848, FieldRCampionSWarrenC Systemic challenge with the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta and IL1beta responses in the diseased brain and exacerbates chronic neurodegeneration. Brain Behav Immun 2010; 24(6): 996–1007.20399848
(ZhangKSchragMCroftonA Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics 2012; 12(8): 1261–1268.22577027)
ZhangKSchragMCroftonA Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics 2012; 12(8): 1261–1268.22577027ZhangKSchragMCroftonA Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics 2012; 12(8): 1261–1268.22577027, ZhangKSchragMCroftonA Targeted proteomics for quantification of histone acetylation in Alzheimer’s disease. Proteomics 2012; 12(8): 1261–1268.22577027
(ParkHGYuHSParkS Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J Neuropsychopharmacol 2014; 17(9): 1487–1500.24606669)
ParkHGYuHSParkS Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J Neuropsychopharmacol 2014; 17(9): 1487–1500.24606669ParkHGYuHSParkS Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J Neuropsychopharmacol 2014; 17(9): 1487–1500.24606669, ParkHGYuHSParkS Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J Neuropsychopharmacol 2014; 17(9): 1487–1500.24606669
J. Stiles, T. Jernigan (2010)
The Basics of Brain DevelopmentNeuropsychology Review, 20
(2017)
Genomewide DNA methylation changes in a mouse model of infectionmediated neurodevelopmental disorders
(LiuXZhaoLYangY Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells. Virology 2014; 464–465: 196–205.)
LiuXZhaoLYangY Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells. Virology 2014; 464–465: 196–205.LiuXZhaoLYangY Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells. Virology 2014; 464–465: 196–205., LiuXZhaoLYangY Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells. Virology 2014; 464–465: 196–205.
(2017)
Genome-wide DNA methylation and transcriptome analyses reveal genes involved in immune responses of pig peripheral blood mononuclear cells to poly I
(IkegameTBundoMSunagaF DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients. Neurosci Res 2013; 77: 208–214.23973796)
IkegameTBundoMSunagaF DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients. Neurosci Res 2013; 77: 208–214.23973796IkegameTBundoMSunagaF DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients. Neurosci Res 2013; 77: 208–214.23973796, IkegameTBundoMSunagaF DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patients. Neurosci Res 2013; 77: 208–214.23973796
M. Penner, Tania Roth, M. Chawla, Lan Hoang, Eric Roth, Farah Lubin, J. Sweatt, Paul Worley, C. Barnes, C. Barnes (2011)
Age-related changes in Arc transcription and DNA methylation within the hippocampusNeurobiology of Aging, 32
(BaghelMSSinghBDhuriyaYK Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain. Neurobiol Learn Mem 2018; 155: 379–389.30195050)
BaghelMSSinghBDhuriyaYK Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain. Neurobiol Learn Mem 2018; 155: 379–389.30195050BaghelMSSinghBDhuriyaYK Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain. Neurobiol Learn Mem 2018; 155: 379–389.30195050, BaghelMSSinghBDhuriyaYK Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brain. Neurobiol Learn Mem 2018; 155: 379–389.30195050
W. Reik (2007)
Stability and flexibility of epigenetic gene regulation in mammalian developmentNature, 447
Kangling Zhang, M. Schrag, A. Crofton, R. Trivedi, H. Vinters, W. Kirsch (2012)
Targeted proteomics for quantification of histone acetylation in Alzheimer's diseasePROTEOMICS, 12
(JanssensSSchotsaertMKarnikR Zika virus alters DNA methylation of neural genes in an organoid model of the developing human brain. mSystems 2018; 3(1): e00219-17.)
JanssensSSchotsaertMKarnikR Zika virus alters DNA methylation of neural genes in an organoid model of the developing human brain. mSystems 2018; 3(1): e00219-17.JanssensSSchotsaertMKarnikR Zika virus alters DNA methylation of neural genes in an organoid model of the developing human brain. mSystems 2018; 3(1): e00219-17., JanssensSSchotsaertMKarnikR Zika virus alters DNA methylation of neural genes in an organoid model of the developing human brain. mSystems 2018; 3(1): e00219-17.
(2010)
Systemic challenge with the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta and IL1beta responses in the diseased brain and exacerbates chronic neurodegeneration
Tania Roth, J. Sweatt (2009)
Regulation of chromatin structure in memory formationCurrent Opinion in Neurobiology, 19
(2012)
for quantification of histone acetylation in Alzheimer ’ s disease
(SilvaPNGigekCOLealMF Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13: 173–176.18376059)
SilvaPNGigekCOLealMF Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13: 173–176.18376059SilvaPNGigekCOLealMF Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13: 173–176.18376059, SilvaPNGigekCOLealMF Promoter methylation analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13: 173–176.18376059
(ZovkicIBGuzman-KarlssonMCSweattJD. Epigenetic regulation of memory formation and maintenance. Learn Mem 2013; 20(2): 61–74.23322554)
ZovkicIBGuzman-KarlssonMCSweattJD. Epigenetic regulation of memory formation and maintenance. Learn Mem 2013; 20(2): 61–74.23322554ZovkicIBGuzman-KarlssonMCSweattJD. Epigenetic regulation of memory formation and maintenance. Learn Mem 2013; 20(2): 61–74.23322554, ZovkicIBGuzman-KarlssonMCSweattJD. Epigenetic regulation of memory formation and maintenance. Learn Mem 2013; 20(2): 61–74.23322554
C. Bramham (2008)
Local protein synthesis, actin dynamics, and LTP consolidationCurrent Opinion in Neurobiology, 18
(PenkeZMoriceEVeyracA. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633): 20130159 http://dx.doi.org/10.1098/rstb.2013.015924298160)
PenkeZMoriceEVeyracA. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633): 20130159 http://dx.doi.org/10.1098/rstb.2013.015924298160PenkeZMoriceEVeyracA. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633): 20130159 http://dx.doi.org/10.1098/rstb.2013.015924298160, PenkeZMoriceEVeyracA. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memory. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633): 20130159 http://dx.doi.org/10.1098/rstb.2013.015924298160
(MizunoMYamadaKTakeiN Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation. Mol Psychiatry 2003; 8(2): 217–224.12610654)
MizunoMYamadaKTakeiN Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation. Mol Psychiatry 2003; 8(2): 217–224.12610654MizunoMYamadaKTakeiN Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation. Mol Psychiatry 2003; 8(2): 217–224.12610654, MizunoMYamadaKTakeiN Phosphatidylinositol 3-kinase: A molecule mediating BDNF-dependent spatial memory formation. Mol Psychiatry 2003; 8(2): 217–224.12610654
(DayJJSweattJD. Epigenetic mechanisms in cognition. Neuron 2011; 70: 813–829.21658577)
DayJJSweattJD. Epigenetic mechanisms in cognition. Neuron 2011; 70: 813–829.21658577DayJJSweattJD. Epigenetic mechanisms in cognition. Neuron 2011; 70: 813–829.21658577, DayJJSweattJD. Epigenetic mechanisms in cognition. Neuron 2011; 70: 813–829.21658577
(FischerSananbenesi FWangX Recovery of learning and memory is associated with chromatin remodeling. Nature 2007; 447: 178–182.17468743)
FischerSananbenesi FWangX Recovery of learning and memory is associated with chromatin remodeling. Nature 2007; 447: 178–182.17468743FischerSananbenesi FWangX Recovery of learning and memory is associated with chromatin remodeling. Nature 2007; 447: 178–182.17468743, FischerSananbenesi FWangX Recovery of learning and memory is associated with chromatin remodeling. Nature 2007; 447: 178–182.17468743
(StilesJJerniganTL. The basics of brain development. Neuropsychol Rev 2010; 20(4): 327–348.21042938)
StilesJJerniganTL. The basics of brain development. Neuropsychol Rev 2010; 20(4): 327–348.21042938StilesJJerniganTL. The basics of brain development. Neuropsychol Rev 2010; 20(4): 327–348.21042938, StilesJJerniganTL. The basics of brain development. Neuropsychol Rev 2010; 20(4): 327–348.21042938
(BramhamCR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008; 18: 524–531.18834940)
BramhamCR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008; 18: 524–531.18834940BramhamCR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008; 18: 524–531.18834940, BramhamCR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008; 18: 524–531.18834940
J. Guan, S. Haggarty, E. Giacometti, J. Dannenberg, Nadine Joseph, Jun Gao, T. Nieland, Ying Zhou, Xinyu Wang, Ralph Mazitschek, J. Bradner, R. DePinho, R. Jaenisch, L. Tsai (2009)
HDAC2 negatively regulates memory formation and synaptic plasticityNature, 459
C. Griñán-Ferré, Sara Sarroca, A. Ivanova, D. Puigoriol-Illamola, F. Aguado, A. Camins, C. Sanfeliu, M. Pallàs (2016)
Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD miceAging (Albany NY), 8
S. Carter, K. Mifsud, J. Reul (2015)
Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze trainingFrontiers in Behavioral Neuroscience, 9
Ulrike Weber-Stadlbauer (2017)
Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disordersTranslational Psychiatry, 7
(LopezPYKenisGStettingerW Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain. Mol Biol Rep 2016; 43: 711–717.27216537)
LopezPYKenisGStettingerW Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain. Mol Biol Rep 2016; 43: 711–717.27216537LopezPYKenisGStettingerW Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain. Mol Biol Rep 2016; 43: 711–717.27216537, LopezPYKenisGStettingerW Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brain. Mol Biol Rep 2016; 43: 711–717.27216537
(IrvineRALinIGHsiehCL. DNA methylation has a local effect on transcription and histone acetylation. Mol Cell Biol 2002; 22: 6689–6696.12215526)
IrvineRALinIGHsiehCL. DNA methylation has a local effect on transcription and histone acetylation. Mol Cell Biol 2002; 22: 6689–6696.12215526IrvineRALinIGHsiehCL. DNA methylation has a local effect on transcription and histone acetylation. Mol Cell Biol 2002; 22: 6689–6696.12215526, IrvineRALinIGHsiehCL. DNA methylation has a local effect on transcription and histone acetylation. Mol Cell Biol 2002; 22: 6689–6696.12215526
(HendrickxPierrot NTasiauxB Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One 2014; 9(6): e99467.24919190)
HendrickxPierrot NTasiauxB Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One 2014; 9(6): e99467.24919190HendrickxPierrot NTasiauxB Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One 2014; 9(6): e99467.24919190, HendrickxPierrot NTasiauxB Epigenetic regulations of immediate early genes expression involved in memory formation by the amyloid precursor protein of Alzheimer disease. PLoS One 2014; 9(6): e99467.24919190
R. Field, S. Campion, C. Warren, C. Murray, C. Cunningham (2010)
Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNα/β and IL-1β responses in the diseased brain and exacerbates chronic neurodegenerationBrain, Behavior, and Immunity, 24
Yara Lopez, G. Kenis, Waldtraud Stettinger, K. Neumeier, S. Jonge, H. Steinbusch, P. Zill, D. Hove, A. Myint (2016)
Effects of prenatal Poly I:C exposure on global histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activity in the mouse brainMolecular Biology Reports, 43
R. Irvine, I. Lin, C. Hsieh (2002)
DNA Methylation Has a Local Effect on Transcription and Histone AcetylationMolecular and Cellular Biology, 22
Jorge Landgrave-Gómez, O. Mercado-Gómez, R. Guevara-Guzmán (2015)
Epigenetic mechanisms in neurological and neurodegenerative diseasesFrontiers in Cellular Neuroscience, 9
(ReikW. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425–432.17522676)
ReikW. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425–432.17522676ReikW. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425–432.17522676, ReikW. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425–432.17522676
J. Levenson, T. Roth, F. Lubin, Courtney Miller, I-Chia Huang, P. Desai, Lauren Malone, D. Sweatt (2006)
Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus*Journal of Biological Chemistry, 281
(LevensonJMRothTLLubinFD Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 2006; 281: 15763–15773.16606618)
LevensonJMRothTLLubinFD Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 2006; 281: 15763–15773.16606618LevensonJMRothTLLubinFD Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 2006; 281: 15763–15773.16606618, LevensonJMRothTLLubinFD Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus. J Biol Chem 2006; 281: 15763–15773.16606618
(HuangZZhouTSunX Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation. Cell Death Differ 2018; 25(1):180–189.28885615)
HuangZZhouTSunX Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation. Cell Death Differ 2018; 25(1):180–189.28885615HuangZZhouTSunX Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation. Cell Death Differ 2018; 25(1):180–189.28885615, HuangZZhouTSunX Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation. Cell Death Differ 2018; 25(1):180–189.28885615
Xia Liu, L. Zhao, Yongtao Yang, L. Bode, Hua Huang, Chengyu Liu, Rongzhong Huang, Liang Zhang, Xiao Wang, Lujun Zhang, Siwen Liu, Jing-jing Zhou, Xin Li, Tieming He, Zhongyi Cheng, P. Xie (2014)
Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cellsVirology, 464
Tempei Ikegame, M. Bundo, Fumiko Sunaga, Tatsuro Asai, Fumichika Nishimura, Akane Yoshikawa, Y. Kawamura, H. Hibino, Mamoru Tochigi, C. Kakiuchi, Tsukasa Sasaki, Tadafumi Kato, K. Kasai, K. Iwamoto (2013)
DNA methylation analysis of BDNF gene promoters in peripheral blood cells of schizophrenia patientsNeuroscience Research, 77
(RichettoJMassartRWeber-StadlbauerU Genome-wide DNA methylation changes in a mouse model of infection-mediated neurodevelopmental disorders. Biol Psychiatry 2017; 81(3): 265–276.27769567)
RichettoJMassartRWeber-StadlbauerU Genome-wide DNA methylation changes in a mouse model of infection-mediated neurodevelopmental disorders. Biol Psychiatry 2017; 81(3): 265–276.27769567RichettoJMassartRWeber-StadlbauerU Genome-wide DNA methylation changes in a mouse model of infection-mediated neurodevelopmental disorders. Biol Psychiatry 2017; 81(3): 265–276.27769567, RichettoJMassartRWeber-StadlbauerU Genome-wide DNA methylation changes in a mouse model of infection-mediated neurodevelopmental disorders. Biol Psychiatry 2017; 81(3): 265–276.27769567
(Weber-StadlbauerU. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders. Transl Psychiatry 2017; 7(5): e1113.28463237)
Weber-StadlbauerU. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders. Transl Psychiatry 2017; 7(5): e1113.28463237Weber-StadlbauerU. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders. Transl Psychiatry 2017; 7(5): e1113.28463237, Weber-StadlbauerU. Epigenetic and transgenerational mechanisms in infection-mediated neurodevelopmental disorders. Transl Psychiatry 2017; 7(5): e1113.28463237
(LuHLiuXDengY DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci 2013; 5: 85.24367332)
LuHLiuXDengY DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci 2013; 5: 85.24367332LuHLiuXDengY DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci 2013; 5: 85.24367332, LuHLiuXDengY DNA methylation, a hand behind neurodegenerative diseases. Front Aging Neurosci 2013; 5: 85.24367332
Makoto Mizuno, Kiyofumi Yamada, Nobuyuki Takei, M. Tran, Jue He, Akira Nakajima, Hiroyuki Nawa, Toshitaka Nabeshima (2003)
Phosphatidylinositol 3-kinase: a molecule mediating BDNF-dependent spatial memory formationMolecular Psychiatry, 8
Padmanabh Singh, M. Thakur (2017)
Histone Deacetylase 2 Inhibition Attenuates Downregulation of Hippocampal Plasticity Gene Expression during AgingMolecular Neurobiology, 55
Haoyang Lu, Xinzhou Liu, Yulin Deng, H. Qing (2013)
DNA methylation, a hand behind neurodegenerative diseasesFrontiers in Aging Neuroscience, 5
Zijing Huang, Tian Zhou, Xiaowei Sun, Yingfeng Zheng, B. Cheng, Mei Li, Xialin Liu, Chang He (2018)
Necroptosis in microglia contributes to neuroinflammation and retinal degeneration through TLR4 activation.Cell death and differentiation, 25 1
C. Dulac (2010)
Brain function and chromatin plasticityNature, 465
Somi Kim, B. Kaang (2017)
Epigenetic regulation and chromatin remodeling in learning and memoryExperimental & Molecular Medicine, 49
H. Park, H. Yu, Soyoung Park, Y. Ahn, Y. Kim, Se Kim (2014)
Repeated treatment with electroconvulsive seizures induces HDAC2 expression and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex.The international journal of neuropsychopharmacology, 17 9
Z. Penke, E. Morice, A. Veyrac, Alexandra Gros, C. Chagneau, P. Leblanc, N. Samson, K. Baumgärtel, I. Mansuy, S. Davis, S. Laroche (2014)
Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term spatial recognition memoryPhilosophical Transactions of the Royal Society B: Biological Sciences, 369
(SinghPThakurMK. Histone deacetylase 2 inhibition attenuates downregulation of hippocampal plasticity gene expression during aging. Mol Neurobiol 2017; 55(3): 2432–2442.28364391)
SinghPThakurMK. Histone deacetylase 2 inhibition attenuates downregulation of hippocampal plasticity gene expression during aging. Mol Neurobiol 2017; 55(3): 2432–2442.28364391SinghPThakurMK. Histone deacetylase 2 inhibition attenuates downregulation of hippocampal plasticity gene expression during aging. Mol Neurobiol 2017; 55(3): 2432–2442.28364391, SinghPThakurMK. Histone deacetylase 2 inhibition attenuates downregulation of hippocampal plasticity gene expression during aging. Mol Neurobiol 2017; 55(3): 2432–2442.28364391
I. Zovkic, Mikael Guzman-Karlsson, J. Sweatt (2013)
Epigenetic regulation of memory formation and maintenance.Learning & memory, 20 2
M. Bradford (1976)
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Analytical biochemistry, 72
(Landgrave-GómezJMercado-GómezOGuevara-GuzmánR. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci 2015; 27: 58.)
Landgrave-GómezJMercado-GómezOGuevara-GuzmánR. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci 2015; 27: 58.Landgrave-GómezJMercado-GómezOGuevara-GuzmánR. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci 2015; 27: 58., Landgrave-GómezJMercado-GómezOGuevara-GuzmánR. Epigenetic mechanisms in neurological and neurodegenerative diseases. Front Cell Neurosci 2015; 27: 58.
(LiWYChangYCLeeLJ Prenatal infection affects the neuronal architecture and cognitive function in adult mice. Dev Neurosci 2014; 36: 359–370.24942872)
LiWYChangYCLeeLJ Prenatal infection affects the neuronal architecture and cognitive function in adult mice. Dev Neurosci 2014; 36: 359–370.24942872LiWYChangYCLeeLJ Prenatal infection affects the neuronal architecture and cognitive function in adult mice. Dev Neurosci 2014; 36: 359–370.24942872, LiWYChangYCLeeLJ Prenatal infection affects the neuronal architecture and cognitive function in adult mice. Dev Neurosci 2014; 36: 359–370.24942872
(Griñán-FerréCSarrocaSIvanovaA Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY) 2016; 8(4): 664–684.27013617)
Griñán-FerréCSarrocaSIvanovaA Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY) 2016; 8(4): 664–684.27013617Griñán-FerréCSarrocaSIvanovaA Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY) 2016; 8(4): 664–684.27013617, Griñán-FerréCSarrocaSIvanovaA Epigenetic mechanisms underlying cognitive impairment and Alzheimer disease hallmarks in 5XFAD mice. Aging (Albany NY) 2016; 8(4): 664–684.27013617
J. Richetto, R. Massart, U. Weber-Stadlbauer, M. Szyf, M. Riva, U. Meyer (2017)
Genome-wide DNA Methylation Changes in a Mouse Model of Infection-Mediated Neurodevelopmental DisordersBiological Psychiatry, 81
Paul Henman (2004)
Targeted!International Sociology, 19
A. Hendrickx, Nathalie Pierrot, B. Tasiaux, O. Schakman, P. Kienlen-Campard, C. Smet, J. Octave (2014)
Epigenetic Regulations of Immediate Early Genes Expression Involved in Memory Formation by the Amyloid Precursor Protein of Alzheimer DiseasePLoS ONE, 9
(2015)
Hippocampal chromatinmodifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment
M. Baghel, Brijendra Singh, Y. Dhuriya, R. Shukla, N. Patro, V. Khanna, I. Patro, M. Thakur (2018)
Postnatal exposure to poly (I:C) impairs learning and memory through changes in synaptic plasticity gene expression in developing rat brainNeurobiology of Learning and Memory, 155
Padmanabh Singh, Arpita Konar, Ashish Kumar, Sweta Srivas, M. Thakur (2015)
Hippocampal chromatin‐modifying enzymes are pivotal for scopolamine‐induced synaptic plasticity gene expression changes and memory impairmentJournal of Neurochemistry, 134
(GuanJSHaggartySJGiacomettiE HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459(7243): 55–60.19424149)
GuanJSHaggartySJGiacomettiE HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459(7243): 55–60.19424149GuanJSHaggartySJGiacomettiE HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459(7243): 55–60.19424149, GuanJSHaggartySJGiacomettiE HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009; 459(7243): 55–60.19424149
(SinghPKonarAKumarA Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment. J Neurochem 2015; 134: 642–651.25982413)
SinghPKonarAKumarA Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment. J Neurochem 2015; 134: 642–651.25982413SinghPKonarAKumarA Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment. J Neurochem 2015; 134: 642–651.25982413, SinghPKonarAKumarA Hippocampal chromatin-modifying enzymes are pivotal for scopolamine-induced synaptic plasticity gene expression changes and memory impairment. J Neurochem 2015; 134: 642–651.25982413
Jeremy J. Day, J. Sweatt (2011)
Epigenetic Mechanisms in CognitionNeuron, 70
Background: Exposure to adverse environmental conditions such as toxic chemicals, viral infections, and even stress during pregnancy or early life may disrupt the development of normal brain and its functioning leading to incidence of neurodevelopmental disorders at later stages of life. Recently, we reported that poly (I:C) exposure altered synaptic plasticity protein level and impaired memory through activation of microglia cells. Purpose: As epigenetic modifications are involved in memory formation, we have studied methylation of DNA and acetylation of histone at promoters of synaptic plasticity genes in the brain of rats exposed to poly (I:C) during early life. Methods: One dose of poly (I:C) (5 mg/kg bw) was intraperitoneally injected to rat pups on postnatal seventh day. A set of pups exposed to vehicle was included as control. In order to assess methylation of DNA and acetylation of histone at synaptic plasticity gene promoter, we performed qPCR after methylated DNA immunoprecipitation and chromatin immunoprecipitation. Results: Poly (I:C) exposure reduced the level of 5-methylcytosine (5mC) at synaptic plasticity gene (bdnf, arc, and egr1) promoters in the frontal cortex (FC) and hippocampus of 3-week rats, although increased it later in both regions of 12-week rats as compared to respective controls. On contrary, poly (I:C) exposure enhanced acetylation of histone H3K9 (H3K9Ac) at promoters of these genes in both regions of 3-week rats but decreased in 12-week rats. Conclusion: Poly (I:C) exposure altered 5mC and H3K9Ac at synaptic plasticity gene promoters resulting in memory impairment of rats at later life. Keywords Poly (I:C), epigenetic modification, gene expression, DNA methylation, histone acetylation, brain development Abbreviation AD, Alzheimer’s disease; ARC, activity-regulated cytoskeleton-associated protein; BDNF, brain derived neurotrophic factor; ChIP, chromatin immunoprecipitation; DNMTs, DNA methyltransferases; EGR1, early growth response 1; FC, frontal cortex; HATs, histone acetyl transferases; HDACs, histone deacetylases; HP, hippocampus 5-mC 5-methyl cytosine; MeDIP, methylated DNA immunoprecipitation; NARP, neuro activity regulated pentaxin; PND, postnatal day; Poly (I:C), polyinosinic-polycytidylic acid; qPCR, quantitative polymerase chain reaction Introduction Department of Zoology, Banaras Hindu University, Varanasi, India. School of Studies in Neuroscience, Jiwaji University, Gwalior, India. Brain development is a tightly regulated programmed process, CSIR—Indian Institute of Toxicology Research, Lucknow, India. which includes cellular events like proliferation, migration, Corresponding author: differentiation, and synapse formation. Prenatal exposure Mahendra Kumar Thakur, Professor, Department of Zoology, Institute of to adverse environmental conditions like toxic chemicals, Science, Banaras Hindu University, Varanasi 221005, India. E-mail: mktian2007@gmail.com viral infections, and even maternal stress during pregnancy Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution- NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-Commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 36 Annals of Neurosciences 26(3–4) negatively affects brain development and its function leading to neurodevelopmental disorders such as autism and schizophrenia in late life. Our previous study showed impairment of learning and memory through activation of microglia and alteration in the level of expression of synaptic plasticity related proteins (BDNF, Arc, EGR1) in the frontal cortex (FC) and hippocampus (HP) of rats exposed to poly (I:C). Highly activated microglia produce inflammatory Figure 1. Timeline of the Experiments: Exposure to Poly (I:C) Was cytokines and induce neuronal apoptosis. In addition, poly Given on PND7 and Methylation of DNA as well as Acetylation of (I:C) exposure triggers the apoptosis signaling leading Histone Were Analyzed in the Brain of 3-, 6-, and 12-week Rats to degeneration of neurons and subsequently deficits in Source: Author’s own. cognitive function including memory. On the other hand, it is reported that viral infection alters 5mC and histone Analysis of Epigenetic Modifications acetylation, which in turn affects gene expression leading to 6–9 10 neurodevelopmental disorders. Singh and Thakur have Following poly (I:C) administration, rats were sacrificed at also shown that variation in epigenetic modifications changes different age of 3-, 6-, and 12-week and FC and HP were the synaptic plasticity gene expression in cerebral cortex as isolated and used for the analysis of epigenetic modifications. well as HP of aged mice. Methylation of DNA and acetylation of histone Methylated DNA Immunoprecipitation (MeDIP) play a major role in regulation of chromatin remodeling, 11–13 The levels of 5mC at bdnf, arc, and egr1 promoters were gene expression, and memory formation. They have analyzed by MeDIP. Initially, we isolated DNA from FC also important functions in normal aging and associated and HP of control and poly (I:C) exposed rats by the phenol- neurodegenerative diseases. For DNA methylation, DNA chloroform-isoamyl alcohol (PCI) method. Then DNA was methyltransferases (DNMTs) transfer methyl groups to fifth fragmented (300–1,000bp) by sonication and quantified using carbon of cytosine at CpG sites. In case of histone acetylation, a spectrophotometer. A small fraction (20%) of fragmented histone transferases (HATs) transfer acetyl groups to histone DNA was used as input DNA control. Thereafter 4 μg tails and histone deacetylases (HDACs) remove them. fragmented DNA was diluted in 1× immunoprecipitation These epigenetic modification machineries are sensitive to medium and incubated overnight with 1 μg of 5mC antibody environmental stimulus. Earlier reports have shown that poly (A-1014; Epigentek, USA) for immunoprecipitation on ice (I:C) alters methylation of DNA and acetylation of histones in with shaking. Then, 50 μl protein A-bead was mixed and 17, 18 brain as well as immune cells. incubated on ice with shaking for 2 h. Further, the precipitated These evidences advocate that poly (I:C) exposure complex bound with beads was setteled down by centrifugation during early life might alter the expression of synaptic at 3,500 ×g at 4°C for 10 min. After careful removal of genes through modulation of epigenetic modifications and supernatant, the pellet was washed with 1× TE buffer atleast lead to memory deficits. This has prompted us to analyze three times followed by centrifugation. Finally, 200 μl elution methylation of DNA and acetylation of histone at synaptic buffer (100 mM NaHCO and 1% SDS) was added to the plasticity gene promoters in the FC as well as HP of 3-, 6-, precipitated complex, DNA was precipitated, purified, and and 12-week rats. further dissolved in equal 20 μl TE buffer for each experimental group. Thereafter, qPCR was performed using eluted and input DNA (for normalization) as template and promoter specific Methods primers to amplify specific promoter regions, 134 nucleotides of bdnf (F-5¢ -TGATCATCACTCACGACCACG-3¢ , R-5¢ - Animals and Poly (I:C) Injection CAGCCTCTCTGAGCCAGTTACG-3¢ ), 91 nucleotides of arc (F-5¢ -GGGTGGCTCTGAAGAATATTGG-3¢ , R-5¢ - Wistar rats were maintained in animal colony at School of CACCGAGCCCTGTTTGAACT-3¢ ), and 120 nucleotides Studies in Neuroscience, Jiwaji University, Gwalior. Poly of egr1 (F-5¢ -ACCACCCAACATCAGCTCTC-3¢ , R-5¢ - (I:C) was administered to rat pups on postnatal day (PND) GTGGGTGAGTGAGGAAAGGA-3¢ ). seven as described previously. All the experiments were performed according to the instructions of Committee for Chromatin Immunoprecipitation (ChIP) the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), and approval of the Institutional ChIP was performed to analyze H3K9 acetylation at histone Animal Ethical Committee, Jiwaji University, Gwalior. bound to gene promoter sequence. Briefly, the FC and HP The schematic timeline for drug administration and other tissues were removed from the brain of experimental and molecular experiments is presented in Figure 1. control rats. Then tissues were chopped into small pieces Baghel et al. 37 precipitated and input fraction by the PCI method. Finally, in ice cold 1 × PBS and crosslinked with 1% formaldehyde these eluted and input DNA served as template for PCR at 25°C for 15 min. Thereafter, crosslinked tissues were amplification of gene promoter region using specific primers homogenized in lysis buffer (5 mM KOH pH 8.0, 85 mM as described above. KCl, 0.5% NP-40 with 1 mM protease inhibitors), kept at 4°C for 5 min, and spun at 1,000 × g at 4°C for 5 min. After decanting supernatant, the pellet was dissolved in Statistical Analysis nuclear lysis buffer (50 mM Tris-Cl pH 8.0, 10 mM EDTA pH 8.0, 1% SDS with 1 mM protease inhibitors) followed by The data obtained from MeDIP and ChIP qPCR assay were incubation at 4°C for 20 min and centrifugation at 12,000 × g statistically analyzed by SPSS 16.0 (Statistical Products and for 15 min to settle the debris. The chromatin complex Service Solutions, IBM Corporation, Armonk, NY, USA) present in supernatant was stored in a fresh tube and protein to check the significant mean difference between control was estimated by the Bradford method. Furthermore, we and experimental groups. The p < .05 was considered as diluted 200 μg chromatin in buffer containing 100 mM NaCl, statistically significant. Histogram was plotted with mean 20 mM Tris-Cl pH 8.0, 2 mM EDTA, pH 8.0, 1% Triton ± SEM values to display the difference between poly (I:C) X-100 with 1 mM protease inhibitors. The diluted chromatin exposed experimental and control rats. complex was incubated with protein A-sepharose beads for 2 h for preclearing step to remove non-specific binding with beads and spun at 3,500 × g for 10 min. The precleared Results supernatant was transferred to a fresh tube and divided into input (20%) and immunoprecipitation fraction (80%). The Effect on DNA Methylation immunoprecipitation fraction was incubated with H3K9Ac Alteration in 5mC level at gene promoter region tightly antibody (1 μg) overnight on ice. Then, protein A bead (50 regulates its expression. To check this, we performed MeDIP- μl) was added to it and kept for further incubation for 2 h PCR of promoter sequence of bdnf, arc, and egr1 genes. As on ice followed by centrifugation at 3,500 ×g for 10 min compared to vehicle control, a significant decrease was noted at 4°C. The supernatant was removed carefully, and pellet in 5mC level at the promoters of these genes in FC and HP was washed sequentially with different solutions (low salt, regions of poly (I:C) exposed 3- and 6-week rats; except the high salt, LiCl, and TE buffer) followed by centrifugation. arc promoter of 6-week rats which showed no difference in Thereafter, the precipitated complex was eluted with buffer methylation level. However, in poly (I:C) exposed 12-week (100 mM NaHCO and 1% SDS), mixed with 200 mM NaCl rats, 5mC level was increased in both regions as compared to and incubated at 65°C for 4 h to reverse the cross-linking control (Figure 2). of protein-DNA complex. Then DNA was isolated from the Figure 2. Analysis of Methylation Level of DNA by MeDIP-PCR at BDNF, Arc, and EGR1 Promoters in FC and HP of Postnatal 3-, 6-, and 12-week Rats. Fold Change in DNA Methylation Level of Experimental Group as Compared to Control is Shown as Mean ± SEM in the Histogram. “*” Indicates Significance in Difference (p < .05) between Poly (I:C) Exposed and Control Animals Source: Author’s own. 38 Annals of Neurosciences 26(3–4) machinery, DNA methylation is involved in the development Effect on Histone Acetylation of neural system, cognitive functions, neurodevelopmental We have also analyzed histone H3K9Ac status at the promoter 23–25 disorders and neurodegenerative diseases. Alteration in of these genes. The exposure to poly (I:C) significantly 5mC level is one of the causal factors for aging and related increased the H3K9Ac level at bdnf, arc, and egr1 promoter neurodegenerative diseases like AD. in both regions of 3-week rats. However, in 6-week, H3K9Ac We have found differential methylation pattern at the level was increased at bdnf promoter in both regions but promoter of bdnf, arc, and egr1 genes in FC as well as HP of increased at arc promoter in FC and decreased in HP. poly (I:C) exposed rats. It was initially increased in both brain Similarly, H3K9Ac at promoter of egr1 decreased in FC and regions of 3- and 6-week but later decreased in 12-week rats. In increased in HP of poly (I:C) exposed 6-week rats. Further, our previous publication, we reported that poly (I:C) injection it decreased at the promoter of these genes in both regions of activated and enhanced TNF-α positive microglia cells after 12 poly (I:C) exposed 12-week rats (Figure 3). h of exposure in hippocampus (HP) and it persisted in 3- and 12-week rats. Interestingly, TNF-α positive cells were less in number in 12-week rats as compared to early age (12 h, 3-week). Discussion Moreover, Zhao et al have shown that the treatment of TNF-α decreases methylation level at IL-32 promoter and upregulates In the current investigation, we have analyzed epigenetic its expression in cell lines. This decreased methylation continues regulation of differentially expressed synaptic plasticity upto 30 days after the withdrawal of treatment, but thereafter genes during postnatal exposure of poly (I:C) to developing it increases leading to decrease in the expression of IL-32 rats. Poly (I:C) has been reported to cause cognitive deficits expression. Thus, TNF-α level might be playing a crucial role and alterations in epigenetic modifications leading to 6, 8, 9 in decreasing DNA methylation initially in 3- and 6-week when neurological disorders. Therefore, it was likely that poly (I:C) affects the epigenetic regulation of synaptic plasticity the TNF-α level is high but increasing methylation in 12-week genes and consequently impairs memory. In epigenetic rats when the TNF-α level is relatively low. Figure 3. Analysis of Histone H3K9 Acetylation Level by ChIP-qPCR at BDNF, Arc, and EGR1 Promoters in FC and HP of Postnatal 3-, 6-, and 12-week rats. Fold Change in Acetylation Level of Experimental Group as Compared to Control is Shown as Mean ± SEM in Histogram. “*” Indicates Significance in Difference (p < .05) between Poly (I:C) Exposed and Control Animals Source: Author’s own. Baghel et al. 39 Methylation pattern also corroborates with the expression pattern of these genes. Similarly, alterations in DNA methylation and histone acetylation at bdnf, arc, egr1, homer1, and narp promoters influence their expression in the brain of aged and scopolamine-induced amnesic mice. DNA methylation recruits the suppressor complex at promoter and prevents the interaction of transcription factors, thus reducing gene transcription. DNA methylation and demethylation events are important for synaptic plasticity and memory consolidation. The inhibition of DNMT enzyme altered the level of DNA methylation and promoted the expression of synaptic plasticity reelin and bdnf genes in adult brain. Hypermethylation of bdnf promoter resulted in its downregulation in schizophrenic patients. In addition, Penner et al have shown that alterations in arc expression and its promoter methylation are associated with impairment in spatial Figure 4. Graphical Representation of Work: Exposure to Poly memory. Our results suggest that differential methylation (I:C) Enhanced Methylation of DNA and Reduced Acetylation of status at promoter affects bdnf, arc, and egr1 expression in Histones with Increasing Age Leading to Changes in Synaptic Plas- poly (I:C) induced infection. The balanced expression of ticity Gene Expression and Thereby Impairment of Memory. BDNF is critical for synaptic plasticity, synaptogenesis, Source: Author’s own. and formation of memory. Arc is an important activity dependent cytoskeleton associated protein, which helps in Acknowledgements actin polymerization, synaptogenesis, long term potentiation, This work was conducted by three research centers under a dendritic arborization, and memory consolidation. EGR1 is collaborative project supported by the Department of Biotechnology a member of immediate early gene and transcription factor, (DBT), Ministry of Science and Technology, Government of India which regulates expression of different synaptic plasticity (BT/PR14311/MED/30/470/2010). We acknowledge UGC-UPE genes. Any imbalance in the expression of these genes impairs FA-II, and Interdisciplinary School of Life Sciences for qPCR their associated functions leading to abnormal behavior and facility; UGC-CAS in Zoology, Banaras Hindu University, Varanasi cognitive functions including memory. Moreover, poly (I:C) for SRF to MSB, and DBT-BET JRF program for DBT-SRF to BS. exposure to pregnant females reduces dendritic complexity and spine density leading to cognitive impairment. Author Contributions Methylated DNA recruits HDAC2 repressor complex, MS Baghel, N Patro, VK Khanna, IK Patro, and MK Thakur: which removes acetyl group and regulates H3K9Ac level. planned and designed the experiments. Histone acetylation is crucial for memory acquisition and B Singh: Conducted poly (I:C) treatment and collected consolidation. Therefore, we have analyzed H3K9 acetylation tissue samples. level and found that in the promoter of bdnf, arc, and egr1 MS Baghel: Carried out experiments, analysed data and genes, H3K9 acetylation increased in the beginning at 3-week drafted the manuscript. and later decreased at 12-week in FC and HP of poly (I:C) VK Khanna, IK Patro, and MK Thakur: Edited the exposed rats. Acetylation level positively correlates with 3 manuscript and corresponded with the journal. the expression pattern of these genes. Poly (I:C) also alters histone acetylation by enhancing HDAC level. Moreover, Ethical Statement Fischer et al have demonstrated increase in the acetylation of H3K9 and H3K14 with enrichment of environmental The maintenance and experimental protocols were approved by factors and recovery of memory in neurodegenerative disease the Institutional Animal Ethical Committee, Jiwaji University, model. H3 and H4 acetylation also decreases at egr1, c-fos, Gwalior (Ref. no. IAEC/JU/2010/02) and carried out according 37–39 to the instructions of Committee for the Purpose of Control and and bdnf promoter in AD. Supervision of Experiments on Animals (CPCSEA). Conclusion Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to Our findings show that the influence of poly (I:C) exposure the research, authorship and/or publication of this article. during early life also persists in later stages. The poly (I:C) exposure alters methylation of DNA and acetylation of histones Funding at synaptic plasticity gene promoters and subsequently affects gene expression in FC and HP regions of rats even at later The authors disclosed receipt of the following financial support for ages leading to impaired memory (Figure 4). the research, authorship and/or publication of this article: Department 40 Annals of Neurosciences 26(3–4) of Biotechnology (DBT), Ministry of Science and Technology, 15. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively Government of India (BT/PR14311/MED/30/470/2010). regulates memory formation and synaptic plasticity. Nature 2009; 459(7243): 55–60. References 16. Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 2007; 447(7143): 425–432. 1. Stiles J, Jernigan TL. The basics of brain development. 17. Lopez PY, Kenis G, Stettinger W, et al. Effects of prenatal Poly Neuropsychol Rev 2010; 20(4): 327–348. I:C exposure on global histone deacetylase (HDAC) and DNA 2. Kundakovic M, Jaric I. The epigenetic link between prenatal methyltransferase (DNMT) activity in the mouse brain. Mol adverse environments and neurodevelopmental disorders. Biol Rep 2016; 43: 711–717. Genes (Basel Stiles) 2017; 8(3): pii: E104. 18. Wang H, Wang J, Ning C, et al. Genome-wide DNA methylation 3. Baghel MS, Singh B, Dhuriya YK, et al. Postnatal exposure and transcriptome analyses reveal genes involved in immune to poly (I:C) impairs learning and memory through changes responses of pig peripheral blood mononuclear cells to poly in synaptic plasticity gene expression in developing rat brain. I:C. Sci Rep 2017; 7(1): 9709. Neurobiol Learn Mem 2018; 155: 379–389. 19. Singh P, Konar A, Kumar A, et al. Hippocampal chromatin- 4. Huang Z, Zhou T, Sun X, et al. Necroptosis in microglia modifying enzymes are pivotal for scopolamine-induced contributes to neuroinflammation and retinal degeneration synaptic plasticity gene expression changes and memory through TLR4 activation. Cell Death Differ 2018; 25(1):180–189. impairment. J Neurochem 2015; 134: 642–651. 5. Field R, Campion S, Warren C, et al. Systemic challenge with 20. Carter SD, Mifsud KR, Reul JM. Distinct epigenetic and gene the TLR3 agonist poly (I:C) induces amplified IFNalpha/beta expression changes in rat hippocampal neurons after Morris and IL1beta responses in the diseased brain and exacerbates water maze training. Front Behav Neurosci 2015; 16: 156. chronic neurodegeneration. Brain Behav Immun 2010; 24(6): 21. Park HG, Yu HS, Park S, et al. Repeated treatment with 996–1007. electroconvulsive seizures induces HDAC2 expression 6. Richetto J, Massart R, Weber-Stadlbauer U, et al. Genome- and down-regulation of NMDA receptor-related genes through histone deacetylation in the rat frontal cortex. Int J wide DNA methylation changes in a mouse model of infection- Neuropsychopharmacol 2014; 17(9): 1487–1500. mediated neurodevelopmental disorders. Biol Psychiatry 2017; 81(3): 265–276. 22. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of 7. Janssens S, Schotsaert M, Karnik R, et al. Zika virus alters protein-dye binding. Anal Biochem 1976; 72: 248–254. DNA methylation of neural genes in an organoid model of the 23. Day JJ, Sweatt JD. Epigenetic mechanisms in cognition. developing human brain. mSystems 2018; 3(1): e00219-17. Neuron 2011; 70: 813–829. 8. Weber-Stadlbauer U. Epigenetic and transgenerational 24. Dulac C. Brain function and chromatin plasticity. Nature 2010; mechanisms in infection-mediated neurodevelopmental 465: 728–735. disorders. Transl Psychiatry 2017; 7(5): e1113. 25. Landgrave-Gómez J, Mercado-Gómez O, Guevara-Guzmán R. 9. Liu X, Zhao L, Yang Y, et al. Human borna disease virus infection Epigenetic mechanisms in neurological and neurodegenerative impacts host proteome and histone lysine acetylation in human diseases. Front Cell Neurosci 2015; 27: 58. oligodendroglia cells. Virology 2014; 464–465: 196–205. 26. Silva PN, Gigek CO, Leal MF, et al. Promoter methylation 10. Singh P, Thakur MK. Histone deacetylase 2 inhibition attenuates analysis of SIRT3, SMARCA5, HTERT and CDH1 genes in downregulation of hippocampal plasticity gene expression aging and Alzheimer’s disease. J Alzheimers Dis 2008; 13: during aging. Mol Neurobiol 2017; 55(3): 2432–2442. 173–176. 11. Kim S, Kaang BK. Epigenetic regulation and chromatin 27. Zhao Z, Lan M, Li J, et al. The proinflammatory cytokine TNFα remodeling in learning and memory. Exp Mol Med 2017; induces DNA demethylation-dependent and-independent 49(1): e281. activation of interleukin-32 expression. J Biol Chem 2019; 294: 12. Zovkic IB, Guzman-Karlsson MC, Sweatt JD. Epigenetic 6785–6795. regulation of memory formation and maintenance. Learn Mem 28. Roth TL, Sweatt JD. Regulation of chromatin structure in 2013; 20(2): 61–74. memory formation. Curr Opin Neurobiol 2009; 19: 336–342. 13. Griñán-Ferré C, Sarroca S, Ivanova A, et al. Epigenetic 29. Levenson JM, Roth TL, Lubin FD, et al. Evidence that DNA mechanisms underlying cognitive impairment and Alzheimer (cytosine-5) methyltransferase regulates synaptic plasticity in disease hallmarks in 5XFAD mice. Aging (Albany NY) 2016; the hippocampus. J Biol Chem 2006; 281: 15763–15773. 8(4): 664–684. 30. Ikegame T, Bundo M, Sunaga F, et al. DNA methylation 14. Lu H, Liu X, Deng Y, et al. DNA methylation, a hand behind analysis of BDNF gene promoters in peripheral blood cells of neurodegenerative diseases. Front Aging Neurosci 2013; 5: 85. schizophrenia patients. Neurosci Res 2013; 77: 208–214. Baghel et al. 41 31. Mizuno M, Yamada K, Takei N, et al. Phosphatidylinositol 36. Irvine RA, Lin IG, Hsieh CL. DNA methylation has a local 3-kinase: A molecule mediating BDNF-dependent spatial effect on transcription and histone acetylation. Mol Cell Biol memory formation. Mol Psychiatry 2003; 8(2): 217–224. 2002; 22: 6689–6696. 32. Bramham CR. Local protein synthesis, actin dynamics, and 37. Fischer, Sananbenesi F, Wang X, et al. Recovery of learning LTP consolidation. Curr Opin Neurobiol 2008; 18: 524–531. and memory is associated with chromatin remodeling. Nature 2007; 447: 178–182. 33. Penke Z, Morice E, Veyrac A. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term 38. Zhang K, Schrag M, Crofton A, et al. Targeted proteomics for spatial recognition memory. Philos Trans R Soc Lond B Biol quantification of histone acetylation in Alzheimer’s disease. Sci 2013; 369(1633): 20130159. http://dx.doi.org/10.1098/ Proteomics 2012; 12(8): 1261–1268. rstb.2013.0159 39. Hendrickx, Pierrot N, Tasiaux B, et al. Epigenetic regulations 34. Li WY, Chang YC, Lee LJ, et al. Prenatal infection affects the of immediate early genes expression involved in memory neuronal architecture and cognitive function in adult mice. Dev formation by the amyloid precursor protein of Alzheimer Neurosci 2014; 36: 359–370. disease. PLoS One 2014; 9(6): e99467. 35. Penner MR, Roth TL, Chawla MK, et al. Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011; 32(12): 2198–2210.
Annals of Neurosciences – SAGE
Published: Jul 1, 2019
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