Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4
Open accessAbstract
Stress induces long-lasting changes in neuronal gene expression and cholinergic neurotransmission, but the underlying mechanism(s) are incompletely understood. Here, we report that chromatin structure and histone modifications are causally involved in this transcriptional memory. Specifically, the AChE gene encoding the acetylcholine-hydrolyzing enzyme acetylcholinesterase is known to undergo long-lasting transcriptional and alternative splicing changes after stress. In mice subjected to stress, we identified two alternative 5′ exons that were down-regulated after stress in the hippocampus, accompanied by reduced acetylation and elevated trimethylation of H3K9 at the corresponding promoter. These effects were reversed completely by daily administration of the histone deacetylase (HDAC) inhibitor sodium butyrate for 1 wk after stress. H3K9 hypoacetylation was associated with a selective, sodium butyrate-reversible promoter accumulation of HDAC4. Hippocampal suppression of HDAC4 in vivo completely abolished the long-lasting AChE-related and behavioral stress effects. Our findings demonstrate long-lasting stress-inducible changes in AChE's promoter choices, identify the chromatin changes that support this long-term transcriptional memory, and reveal HDAC4 as a mediator of these effects in the hippocampus.
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The effects of stress on AChE were reversed by an HDAC inhibitor, and reduced hippocampal HDAC4 levels restored the long-lasting behavioral deficit.
“These effects were reversed drastically by administration an HDAC inhibitor, and reduced hippocampal HDAC4 levels restored the long-lasting behavioral deficit.136”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [136]
The AChE gene was downregulated in the hippocampus after stress, accompanied by decreased acetylation and increased H3K9 trimethylation at its promoter and HDAC4 accumulation in hippocampal neurons.
“The AChE gene, which encodes the acetylcholine-hydrolyzing enzyme acetylcholinesterase, was downregulated in the hippocampus after stress and accompanied by decreased acetylation and increased trimethylation of H3K9 at the corresponding promoter, as well as HDAC4 accumulation in hippocampal neurons.”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [136]
Increased hippocampal HDAC4 following chronic stress exposure has been reported, whereas suppression of hippocampal HDAC4 abolished the long-lasting behavioral deficits induced by stress.
“Another study reported increased hippocampal HDAC4 following chronic stress exposure, 84 whereas suppression of hippocampal HDAC4 abolished the long-lasting behavioral deficits induced by stress.”
From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [84]
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Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · see citing works
The use of the elevated plus maze as an assay of anxiety-related behavior in rodents
Walf, A. A., & Frye, C. A. (2007) · Nature Protocols · doi:10.1038/nprot.2007.44 · Cited by 3,035 · see citing works
Histone acetylation in chromatin structure and transcription
Grunstein, M. (1997) · Nature · doi:10.1038/38664 · Cited by 2,884 · see citing works
Histone deacetylases and cancer: causes and therapies
Marks, P. A., Rifkind, R. A., Richon, V. M., Breslow, R., Miller, T., & Kelly, W. K. (2001) · Nature reviews. Cancer · doi:10.1038/35106079 · Cited by 1,866 · see citing works
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
Tsankova, N. M., Berton, O., Renthal, W., Kumar, A., Neve, R. L., & Nestler, E. J. (2006) · Nature Neuroscience · doi:10.1038/nn1659 · Cited by 1,780 · see citing works
Role of Histone H3 Lysine 9 Methylation in Epigenetic Control of Heterochromatin Assembly
Nakayama, J.-I., Rice, J. C., Strahl, B. D., Allis, C. D., & Grewal, S. I. S. (2001) · Science · doi:10.1126/science.1060118 · Cited by 1,739 · see citing works
HDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644 · see citing works
Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit
Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdés-Ferrer, S. I., Levine, Y. A., Reardon, C., Tusche, M. W., Pavlov, V. A., Andersson, U., Chavan, S., et al. (2011) · Science · doi:10.1126/science.1209985 · Cited by 1,551 · see citing works
Inhibition of Histone Deacetylase Activity by Butyrate
Davie, J. R. (2003) · The Journal of Nutrition · doi:10.1093/jn/133.7.2485s · Cited by 1,515 · see citing works
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228 · see citing works
The cellular neurobiology of depression
Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
Regulation of histone acetylation during memory formation in the hippocampus
Levenson, J. M., O'Riordan, K. J., Brown, K. D., Trinh, M. A., Molfese, D. L., & Sweatt, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402229200 · Cited by 1,131 · see citing works
Production and purification of lentiviral vectors
Tiscórnia, G., Singer, O., & Verma, I. M. (2006) · Nature Protocols · doi:10.1038/nprot.2006.37 · Cited by 974 · see citing works
Meaney, M. J., & Szyf, M. (2005) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2005.7.2/mmeaney · Cited by 958 · see citing works
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
Peleg, S., Sananbenesi, F., Zovoilis, A., Burkhardt, S., Bahari-Javan, S., Agis-Balboa, R. C., Cota, P., Wittnam, J. L., Gogol-Doering, A., Opitz, L., et al. (2010) · Science · doi:10.1126/science.1186088 · Cited by 951 · see citing works
Plasticity of the Hippocampus: Adaptation to Chronic Stress and Allostatic Load
McEwen, B. S. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05830.x · Cited by 875 · see citing works
The many faces of histone lysine methylation
Lachner, M., & Jenuwein, T. (2002) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(02)00335-6 · Cited by 814 · see citing works
An epigenetic road map for histone lysine methylation
Lachner, M., O’Sullivan, R. J., & Jenuwein, T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00493 · Cited by 630 · see citing works
Antidepressant Actions of Histone Deacetylase Inhibitors
Covington, H. E., Maze, I., LaPlant, Q. C., Vialou, V. F., Ohnishi, Y. N., Berton, O., Fass, D. M., Renthal, W., Rush, A. J., Wu, E. Y., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1758-09.2009 · Cited by 624 · see citing works
Regulation of transcription factors by neuronal activity
West, A. E., Griffith, E. C., & Greenberg, M. E. (2002) · Nature reviews. Neuroscience · doi:10.1038/nrn987 · Cited by 604 · see citing works
Acute stress facilitates long-lasting changes in cholinergic gene expression
Kaufer, D., Friedman, A., Seidman, S., & Soreq, H. (1998) · Nature · doi:10.1038/30741 · Cited by 588 · see citing works
Self-citationLitt, M. D., Simpson, M., Gaszner, M., Allis, C. D., & Felsenfeld, G. (2001) · Science · doi:10.1126/science.1064413 · Cited by 579 · see citing works
Histone Methylation Regulates Memory Formation
Gupta, S., Kim, S. Y., Artis, S., Molfese, D. L., Schumacher, A., Sweatt, J. D., Paylor, R. E., & Lubin, F. D. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3732-09.2010 · Cited by 562 · see citing works
Guan, Z., Giustetto, M., Lomvardas, S., Kim, J.-H., Miniaci, M. C., Schwartz, J. H., Thanos, D., & Kandel, E. R. (2002) · Cell · doi:10.1016/s0092-8674(02)01074-7 · Cited by 497 · see citing works
Tsankova, N. M., Kumar, A., & Nestler, E. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0589-04.2004 · Cited by 447 · see citing works
MicroRNA-132 Potentiates Cholinergic Anti-Inflammatory Signaling by Targeting Acetylcholinesterase
Shaked, I., Meerson, A., Wolf, Y., Avni, R., Greenberg, D., Gilboa-Geffen, A., & Soreq, H. (2009) · Immunity · doi:10.1016/j.immuni.2009.09.019 · Cited by 416 · see citing works
Self-citationUchida, S., Hara, K., Kobayashi, A., Otsuki, K., Yamagata, H., Hobara, T., Suzuki, T., Miyata, N., & Watanabe, Y. (2011) · Neuron · doi:10.1016/j.neuron.2010.12.023 · Cited by 398 · see citing works
Pathophysiology of depression: the concept of synaptic plasticity
Duman, R. S. (2002) · European Psychiatry · doi:10.1016/s0924-9338(02)00654-5 · Cited by 361 · see citing works
Gene Profile of Electroconvulsive Seizures: Induction of Neurotrophic and Angiogenic Factors
Newton, S. S., Collier, E. F., Hunsberger, J. G., Adams, D., Terwilliger, R. Z., Selvanayagam, E., & Duman, R. S. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-34-10841.2003 · Cited by 355 · see citing works
Distribution of histone deacetylases 1–11 in the rat brain
Broide, R. S., Redwine, J. M., Aftahi, N., Young, W. G., Bloom, F. E., & Winrow, C. J. (2007) · Journal of Molecular Neuroscience · doi:10.1007/bf02686117 · Cited by 347 · see citing works
Regulation of hippocampal H3 histone methylation by acute and chronic stress
Hunter, R. G., McCarthy, K. J., Milne, T. A., Pfaff, D. W., & McEwen, B. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911143106 · Cited by 290 · see citing works
Minamiyama, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh131 · Cited by 260 · see citing works
Crosio, C., Heitz, E., Allis, C. D., Borrelli, E., & Sassone‐Corsi, P. (2003) · Journal of Cell Science · doi:10.1242/jcs.00804 · Cited by 242 · see citing works
Alternative Splicing and Neuritic mRNA Translocation Under Long-Term Neuronal Hypersensitivity
Meshorer, E., Erb, C., Gazit, R., Pavlovsky, L., Kaufer, D., Friedman, A., Glick, D., Ben‐Arie, N., & Soreq, H. (2002) · Science · doi:10.1126/science.1066752 · Cited by 228 · see citing works
Self-citationEpigenetic GABAergic targets in schizophrenia and bipolar disorder
Guidotti, A., Auta, J., Chen, Y., Davis, J. M., Dong, E., Gavin, D. P., Grayson, D. R., Matrisciano, F., Pinna, G., Satta, R., et al. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.10.021 · Cited by 220 · see citing works
Marcaurelle, L. A., Comer, E., Dandapani, S., Duvall, J. R., Gerard, B., Kesavan, S., Lee, M. D., Liu, H., Lowe, J. T., Marié, J., et al. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105119r · Cited by 211 · see citing works
Shaltiel, G., Hanan, M., Wolf, Y., Barbash, S., Kovalev, E., Shoham, S., & Soreq, H. (2012) · Brain Structure and Function · doi:10.1007/s00429-011-0376-z · Cited by 171 · see citing works
Self-citationCombinatorial Complexity of 5′ Alternative Acetylcholinesterase Transcripts and Protein Products
Meshorer, E., Toiber, D., Zurel, D., Sahly, I., Dori, A., Cagnano, E., Schreiber, L., Grisaru, D., Tronche, F., & Soreq, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402752200 · Cited by 111 · see citing works
Self-citationProbing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity
Haggarty, S. J., & Tsai, L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.04.009 · Cited by 99 · see citing works
Maternal Deprivation Stress Exacerbates Cognitive Deficits in Immature Rats with Recurrent Seizures
Huang, L., Holmes, G. L., Lai, M., Hung, P., Wang, C., Wang, T., Yang, C., Liou, C., & Yang, S. N. (2002) · Epilepsia · doi:10.1046/j.1528-1157.2002.14602.x · Cited by 94 · see citing works
SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA
Meshorer, E., Bryk, B., Toiber, D., Cohen, J. E., Podoly, E., Dori, A., & Soreq, H. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001735 · Cited by 83 · see citing works
Self-citationChromatin and nuclear architecture in the nervous system
Takizawa, T., & Meshorer, E. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.03.005 · Cited by 63 · see citing works
Self-citationZimmerman, G., Shaltiel, G., Barbash, S., Cohen, J., Gasho, C. J., Shenhar‐Tsarfaty, S., Shalev, H., Berliner, S. A., Shelef, I., Shoham, S., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.4 · Cited by 55 · see citing works
Self-citationTargeting Histone Deacetylases for the Treatment of Huntington's Disease
Gray, S. G. (2010) · CNS Neuroscience & Therapeutics · doi:10.1111/j.1755-5949.2010.00184.x · Cited by 34 · see citing works
Chromatin Immunoprecipitation in Mouse Hippocampal Cells and Tissues
Sailaja, B. S., Takizawa, T., & Meshorer, E. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-376-9_24 · Cited by 27 · see citing works
Self-citationIng1 Mediates p53 Accumulation and Chromatin Modification in Response to Oncogenic Stress
Abad, M., Menéndez, C., Füchtbauer, A. C., Serrano, M., Füchtbauer, E., & Palmero, I. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701639200 · Cited by 24 · see citing works
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Nigám, S. K., Bush, K. T., Martovetsky, G., Ahn, S.-Y., Liu, H. C., Richard, E., Bhatnagar, V., & Wu, W. (2014) · Physiological Reviews · doi:10.1152/physrev.00025.2013 · Cited by 505 · see citing works
Biological embedding of experience: a primer on epigenetics
Aristizabal, M. J., Anreiter, I., Halldorsdottir, T., Odgers, C. L., McDade, T. W., Goldenberg, A., Mostafavi, S., Kobor, M. S., Binder, E. B., Sokolowski, M. B., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820838116 · Cited by 268 · see citing works
Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“136 In addition, overexpression of HDAC4 in the hippocampus caused adult rats to be depressive but not anxious.”
BackgroundKratsman, N., Getselter, D., & Elliott, E. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.11.003 · Cited by 239 · see citing works
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Wang, Z., Qin, G., & Zhao, T. C. (2014) · Epigenomics · doi:10.2217/epi.13.73 · Cited by 239 · see citing works
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
Chetty, S., Friedman, A., Taravosh-Lahn, K., Kirby, E. D., Mirescu, C., Guo, F., Krupik, D., Nicholas, A., Geraghty, A., Krishnamurthy, A., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.190 · Cited by 245 · see citing works
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Light affects salt stress-induced transcriptional memory of P5CS1 in Arabidopsis
Feng, X., Li, J. R., Qi, S., Lin, Q. F., Jin, J. B., & Hua, X. J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610670114 · Cited by 178 · see citing works
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Higuchi, F., Uchida, S., Yamagata, H., Abe-Higuchi, N., Hobara, T., Hara, K., Kobayashi, A., Shintaku, T., Itoh, Y., Suzuki, T., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0319-16.2016 · Cited by 158 · see citing works
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Soreq, H. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.05.007 · Cited by 117 · see citing works
Self-citationKim, J., Seung, H., Kwon, K. J., Ko, M. J., Lee, E. J., Oh, H. A., Choi, C. S., Kim, K. C., Gonzales, E. L., You, J. S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104927 · Cited by 117 · see citing works
Heat Acclimation, Epigenetics, and Cytoprotection Memory
Horowitz, M. (2014) · Comprehensive physiology · doi:10.1002/cphy.c130025 · Cited by 115 · see citing works
Mielcarek, M., Zielonka, D., Carnemolla, A., Marcinkowski, T., & Guidez, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00042 · Cited by 111 · see citing works
Cardiomyocyte‐secreted acetylcholine is required for maintenance of homeostasis in the heart
Roy, A., Fields, W. C., Resende, C. R., Resende, R. R., Guatimosim, S., Prado, V. F., Gros, R., & Prado, M. A. M. (2013) · The FASEB Journal · doi:10.1096/fj.13-238279 · Cited by 111 · see citing works
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Horowitz, M. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00552.2015 · Cited by 100 · see citing works
de Abreu, M. S., Demin, K. A., Giacomini, A. C. V. V., Amstislavskaya, T. G., Strekalova, T. V., Maslov, G. O., Kositsin, Y., Petersen, E. V., & Kalueff, A. V. (2021) · Neurobiology of Stress · doi:10.1016/j.ynstr.2021.100405 · Cited by 89 · see citing works
Raviv, S., Bharti, K., Rencus‐Lazar, S., Cohen‐Tayar, Y., Schyr, R. B., Evantal, N., Meshorer, E., Zilberberg, A., Idelson, M., Reubinoff, B. E., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004360 · Cited by 88 · see citing works
Self-citationHippocampal HDAC4 Contributes to Postnatal Fluoxetine-Evoked Depression-Like Behavior
Sarkar, A., Chachra, P., Kennedy, P., Pena, C. J., Desouza, L. A., Nestler, E. J., & Vaidya, V. A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.73 · Cited by 79 · see citing works
Sharma, S., Taliyan, R., & Ramagiri, S. (2014) · Journal of Molecular Neuroscience · doi:10.1007/s12031-014-0461-x · Cited by 74 · see citing works
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Shenhar‐Tsarfaty, S., Berliner, S., Bornstein, N. M., & Soreq, H. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0176-4 · Cited by 73 · see citing works
Self-citationMolecular mechanisms of psychiatric diseases
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Zimmermann, M. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12359 · Cited by 58 · see citing works
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Srinivasan, S., Shariff, M. R., & Bartlett, S. E. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00068 · Cited by 61 · see citing works
The Effects of Stress and Meditation on the Immune System, Human Microbiota, and Epigenetics.
Househam, A. M., Peterson, C. T., Mills, P. J., & Chopra, D. (2017) · PubMed · Cited by 57 · see citing works
Elevation of Il6 is associated with disturbed let-7 biogenesis in a genetic model of depression
Wei, Y. B., Liu, J. J., Villaescusa, J. C., Åberg, E., Brené, S., Wegener, G., Mathé, A. A., & Lavebratt, C. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.136 · Cited by 57 · see citing works
Transcription Factors Bind Negatively Selected Sites within Human mtDNA Genes
Blumberg, A., Sailaja, B. S., Kundaje, A. B., Levin, L., Dadon, S., Shmorak, S., Shaulian, E., Meshorer, E., & Mishmar, D. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu210 · Cited by 55 · see citing works
Self-citationDecline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events
Arbel, Y., Shenhar‐Tsarfaty, S., Waiskopf, N., Finkelstein, A., Halkin, A., Revivo, M., Berliner, S. A., Herz, I., Shapira, I., Keren, G., et al. (2013) · Molecular Medicine · doi:10.2119/molmed.2013.00139 · Cited by 54 · see citing works
Self-citationVihervaara, A., Mahat, D. B., Himanen, S. V., Blom, M. A. H., Lis, J. T., & Sistonen, L. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.03.007 · Cited by 52 · see citing works
Liu, W., Pan, Y., Yang, L., Xie, Y. Z., Chen, X., Chang, J., Hao, W., Zhu, L., & Wan, B. (2022) · Journal of Environmental Sciences · doi:10.1016/j.jes.2022.04.022 · Cited by 52 · see citing works
Fetal microglial phenotype in vitro carries memory of prior in vivo exposure to inflammation
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Wu, Y., Hou, F., Wang, X., Kong, Q., Han, X., & Bai, B. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00114 · Cited by 52 · see citing works
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Self-citationYang, L., Wang, J., Wang, D., Hu, G., Liu, Z., Yan, D., Serikuly, N., Alpyshov, E. T., Demin, K. A., Strekalova, T. V., et al. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112644 · Cited by 44 · see citing works
Lin, T.-B., Hsieh, M., Lai, C., Cheng, J., Chau, Y., Ruan, T., Chen, G., & Peng, H. (2015) · Anesthesiology · doi:10.1097/aln.0000000000000663 · Cited by 44 · see citing works
Nätt, D., Johansson, I., Faresjö, T., Ludvigsson, J., & Thorsell, A. (2015) · Clinical Epigenetics · doi:10.1186/s13148-015-0123-z · Cited by 43 · see citing works
Frasch, M. G., Lobmaier, S. M., Stampalija, T., Desplats, P., Pallarés, M. E., Pastor, V. E., Brocco, M. A., Wu, H., Schulkin, J. A., Herry, C. L., et al. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.026 · Cited by 43 · see citing works
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Shenhar‐Tsarfaty, S., Yayon, N., Waiskopf, N., Shapira, I., Toker, S., Zaltser, D., Berliner, S. A., Ritov, Y., & Soreq, H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418264112 · Cited by 42 · see citing works
Self-citationFitzsimons, H. L. (2015) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2015.06.006 · Cited by 41 · see citing works
Central and peripheral anti-inflammatory effects of acetylcholinesterase inhibitors
Vaknine, S., & Soreq, H. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108020 · Cited by 40 · see citing works
Self-citationGezen‐Ak, D., Alaylıoğlu, M., Yurttaş, Z., Çamoğlu, T., Şengül, B., İşler, C., Kina, U. Y., Keskin, E., Atasoy, İ. L., Kafadar, A. M., et al. (2023) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2023.109322 · Cited by 37 · see citing works
Myrzakhanova, M., Gambardella, C., Falugi, C., Gatti, A., Tagliafierro, G., Ramoino, P., Bianchini, P., & Diaspro, A. (2013) · BioMed Research International · doi:10.1155/2013/205183 · Cited by 37 · see citing works
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Tambuwala, M. M. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000655 · Cited by 36 · see citing works
Mallei, A., Ieraci, A., & Popoli, M. (2018) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2018.1500029 · Cited by 35 · see citing works
Pusalkar, M., Suri, D., Kelkar, A., Bhattacharya, A., Galande, S., & Vaidya, V. A. (2015) · Developmental Psychobiology · doi:10.1002/dev.21365 · Cited by 36 · see citing works
Sagarkar, S., Balasubramanian, N., Mishra, S., Choudhary, A. G., Kokare, D. M., & Sakharkar, A. J. (2019) · Brain Research · doi:10.1016/j.brainres.2019.01.022 · Cited by 35 · see citing works
Karen, C., & Rajan, K. E. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-019-00655-x · Cited by 37 · see citing works
Valproic acid potentiates curcumin-mediated neuroprotection in lipopolysaccharide induced rats
Zaky, A., Mahmoud, M., Awad, D., Sabaa, B. M. E., Kandeel, K., & Bassiouny, A. R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00337 · Cited by 34 · see citing works
Cortes, M., Cao, M., Liu, H. L., Moore, C. S., Durosier, L. D., Burns, P., Fecteau, G., Desrochers, A., Barreiro, L. B., Antel, J. P., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-09439-z · Cited by 32 · see citing works
Telencephalon transcriptome analysis of chronically stressed adult zebrafish
Huang, V., Butler, A. A., & Lubin, F. D. (2019) · Scientific Reports · doi:10.1038/s41598-018-37761-7 · Cited by 33 · see citing works
Synaptically Localized Transcriptional Regulators in Memory Formation
Uchida, S., & Shumyatsky, G. P. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.07.023 · Cited by 33 · see citing works
Muñoz-Llanos, M., García-Pérez, M. A., Xu, X., Tejos‐Bravo, M., Vidal, E. A., Moyano, T. C., Gutiérrez, R. A., Aguayo, F. I., Pacheco, A., García‐Rojo, G., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00251 · Cited by 32 · see citing works
The stage-dependent roles of Ldb1 and functional redundancy with Ldb2 in mammalian retinogenesis
Gueta, K., David, A., Cohen, T., Menuchin-Lasowski, Y., Nobel, H., Narkis, G., Li, L., Love, P. E., de Melo, J., Blackshaw, S., et al. (2016) · Development · doi:10.1242/dev.129734 · Cited by 31 · see citing works
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Mielcarek, M., Seredenina, T. S., Stokes, M. P., Osborne, G. F., Landles, C., Inuabasi, L., Franklin, S., Silva, J. C., Luthi‐Carter, R., Beaumont, V., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080849 · Cited by 30 · see citing works
Hayase, T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0158950 · Cited by 25 · see citing works
Moyano, P. M., Flores, A., García, J., García, J. M., Anadón, M. J., Frejo, M. T., Solà, E., Pelayo, A., & del Pino, J. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112614 · Cited by 24 · see citing works
Peng, L., Zhu, M., Yang, Y., Weng, Y., Zou, W., Zhu, X., Guo, Q., & Zhong, T. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.12.001 · Cited by 23 · see citing works
Livyatan, I., & Meshorer, E. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.33 · Cited by 22 · see citing works
Self-citationAutism Spectrum Disorder: A Neuro-Immunometabolic Hypothesis of the Developmental Origins
Frasch, M. G., Yoon, B.-J., Helbing, D. L., Snir, G., Antonelli, M. C., & Bauer, R. (2023) · Biology · doi:10.3390/biology12070914 · Cited by 21 · see citing works
Wolugbom, J. A., Areloegbe, S. E. J., & Olaniyi, K. S. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03074-0 · Cited by 25 · see citing works
Heat Acclimation, Epigenetics, and Cytoprotection Memory
Horowitz, M. (2014) · Comprehensive physiology · doi:10.1002/j.2040-4603.2014.tb00549.x · Cited by 22 · see citing works
New perspectives for multi-level regulations of neuronal acetylcholinesterase by dioxins
Xie, H. Q., Xu, T., Chen, Y., Li, Y., Xia, Y., Xu, S. L., Wang, L., Tsim, K. W. K., & Zhao, B. (2016) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2016.06.030 · Cited by 21 · see citing works
Cao, M., MacDonald, J. W., Liu, H. L., Weaver, M., Cortes, M., Durosier, L. D., Burns, P., Fecteau, G., Desrochers, A., Schulkin, J. A., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01063 · Cited by 20 · see citing works
Apocynin Prevents Abnormal Megakaryopoiesis and Platelet Activation Induced by Chronic Stress
Sandrini, L., Ieraci, A., Amadio, P., Popoli, M., Tremoli, E., & Barbieri, S. S. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/9258937 · Cited by 21 · see citing works
Behavioral stress reduces RIP140 expression in astrocyte and increases brain lipid accumulation
Feng, X., Lin, Y., & Wei, L. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.02.008 · Cited by 20 · see citing works
Xi, Q., Gao, N., Zhang, X., Zhang, B., Ye, W., Wu, J., & Zhang, X. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.09.012 · Cited by 20 · see citing works
Xu, H., Xie, H. Q., Tao, W., Zhou, Z., Li, S.-Z., & Zhao, B. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0167-5 · Cited by 20 · see citing works
Duggan, S. P., Behan, F. M., Kirca, M., Zaheer, A., McGarrigle, S. A., Reynolds, J. V., Vaz, G. M. F., Senge, M. O., & Kelleher, D. P. (2016) · Scientific Reports · doi:10.1038/srep32638 · Cited by 20 · see citing works
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Haviv, R., Oz, E., & Soreq, H. (2017) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0515-z · Cited by 19 · see citing works
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Liu, H., Xia, J., Wang, T., Li, W., Song, Y., & Tan, G. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.03.049 · Cited by 19 · see citing works
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Nadorp, B., & Soreq, H. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.04.058 · Cited by 19 · see citing works
Self-citationCoimbra, B., Soares‐Cunha, C., Borges, S., de Vasconcelos, N. A. P., Sousa, N., & Rodrigues, A. J. (2017) · eLife · doi:10.7554/elife.25843 · Cited by 18 · see citing works
Histone deacetylase 4 (HDAC4): a new player in anorexia nervosa?
Sild, M., & Booij, L. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0366-8 · Cited by 18 · see citing works
Holtkamp, C., Koos, B., Unterberg, M., Rahmel, T., Bergmann, L., Bazzi, Z., Bazzi, M., Bukhari, H., Adamzik, M., & Rump, K. (2019) · PLoS ONE · doi:10.1371/journal.pone.0217269 · Cited by 17 · see citing works
Wu, K. L. H., Liu, W., Wu, C., Fu, M., Huang, H., Tain, Y., Liang, C., Hung, C., Chen, I., Hung, P., et al. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109571 · Cited by 17 · see citing works
Barbieri, S. S., Sandrini, L., Musazzi, L., Popoli, M., & Ieraci, A. (2021) · Biomolecules · doi:10.3390/biom11060885 · Cited by 17 · see citing works
Grafting improves drought stress memory by increasing the P5CS1 gene expression in Brassica rapa
Luo, L., Zheng, Y., Gao, Z., Chen, Q., Kong, X., & Yang, Y. (2020) · Plant and Soil · doi:10.1007/s11104-020-04547-8 · Cited by 16 · see citing works
K V, A., Madhana, R. M., Bais, A. K., Singh, V. B., Malik, A., Sinha, S., Lahkar, M., Kumar, P., & Samudrala, P. K. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00315 · Cited by 15 · see citing works
Waiskopf, N., & Soreq, H. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800159-2.00052-x · Cited by 15 · see citing works
Self-citationZhang, T., Linglin, Z., Zeng, S., Bai, L., Chen, J., Zhang, Z., Wang, Y., & Duan, C. (2016) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2805 · Cited by 14 · see citing works
Ekronarongchai, S., Palaga, T., Saonanon, P., Pruksakorn, V., Hirankarn, N., van Hagen, P. M., Dik, W. A., & Virakul, S. (2021) · Thyroid · doi:10.1089/thy.2020.0948 · Cited by 14 · see citing works
Zhang, L., Chen, C., & Qi, J. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147051 · Cited by 13 · see citing works
HP1BP3 expression determines maternal behavior and offspring survival
Garfinkel, B. P., Arad, S., Neuner, S. M., Netser, S., Wagner, S., Kaczorowski, C. C., Rosen, C. J., Gal, M., Soreq, H., & Orly, J. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12312 · Cited by 13 · see citing works
Self-citationHod, K., Sperber, A. D., Maharshak, N., Ron, Y., Shapira, I., Zeltser, D., Rogowski, O., Berliner, S. A., Shenhar‐Tsarfaty, S., & Dekel, R. (2018) · Neurogastroenterology & Motility · doi:10.1111/nmo.13464 · Cited by 13 · see citing works
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da Silva, A. N., Araújo, M. S., Pértille, F., & Zanella, A. J. (2021) · Animals · doi:10.3390/ani12010032 · Cited by 16 · see citing works
Mohammadi-Farani, A., Limoee, M., & Shirooie, S. (2021) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000633 · Cited by 11 · see citing works
Histone deacetylase inhibition abolishes stress-induced spatial memory impairment
Vargas-López, V., Lamprea, M. R., & Múnera, A. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.08.009 · Cited by 11 · see citing works
Kotova, M. M., Amikishiev, S. V., Apukhtin, K. V., Galstyan, D. S., de Abreu, M. S., Stewart, A., Yang, L., & Kalueff, A. V. (2025) · Journal of Comparative Physiology B · doi:10.1007/s00360-025-01613-4 · Cited by 10 · see citing works
Mohammadi-Farani, A., Farhangian, S., & Shirooie, S. (2022) · Research in Pharmaceutical Sciences · doi:10.4103/1735-5362.359435 · Cited by 9 · see citing works
Brain region-specific effects of immobilization stress on cholinesterases in mice
Valuskova, P., Farár, V., Janisova, K., Ondičová, K., Mravec, B., Květňanský, R., & Mysliveček, J. (2016) · Stress · doi:10.1080/10253890.2016.1263836 · Cited by 9 · see citing works
The effect of sodium channels on neurological/neuronal disorders: A systematic review
Bagheri, S., Haddadi, R., Saki, S., Kourosh‐Arami, M., & Komaki, A. (2021) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10153 · Cited by 8 · see citing works
Omer, D., Cohen-Zontag, O., Gnatek, Y., Harari‐Steinberg, O., Pleniceanu, O., Namestnikov, M., Cohen, A.-H., Nissim‐Rafinia, M., Tam, G., Tomer Kalisky, C., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.04.005 · Cited by 7 · see citing works
Self-citationHistone Deacetylation in Alzheimer’s Diseases (AD); Hope or Hype
Ateya, N. H., Al-Taie, S., Jasim, S., Uthirapathy, S., Chaudhary, K., Rani, P., Kundlas, M., Naidu, K., Amer, N. A. A., & Ahmed, J. K. (2025) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-025-01670-0 · Cited by 5 · see citing works
The Current and Future Role of Drugs and Probiotics in the Management of Inflammatory Bowel Disease
de Souza, M. D. S. S., Barbalho, S. M., Goulart, R. D. Á., & de Carvalho, A. D. C. A. (2015) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2015.38008 · Cited by 7 · see citing works
A non‐adaptationist hypothesis of play behaviour
Lewis, A. (2023) · The Journal of Physiology · doi:10.1113/jp284413 · Cited by 7 · see citing works
Pesticide tolerance induced by a generalized stress response in wood frogs (Rana sylvatica)
Billet, L. S., & Hoverman, J. T. (2020) · Ecotoxicology · doi:10.1007/s10646-020-02277-2 · Cited by 7 · see citing works
Role of histone deacetylases in neuroplasticity impairments and inflammation in major depression
Garayo, A., Azqueta, A., & Tordera, R. M. (2024) · Neuroscience Applied · doi:10.1016/j.nsa.2024.104081 · Cited by 7 · see citing works
Kniffin, A. R., Bangasser, D. A., & Parikh, V. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.15999 · Cited by 6 · see citing works
- Authors
- Sailaja, B. S., Cohen-Carmon, D., Zimmerman, G., Soreq, H., & Meshorer, E.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Departments of aGenetics and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-12-10
- Volume
- 109
- Issue
- 52
- Pages
- E3687-95
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3535662
- OpenAlex
- W2102812580
- Cited by
- 121
- References
- 47
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 10 · 2023: 7 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 10 · 2018: 5 · 2017: 10 · 2016: 14 · 2015: 14 · 2014: 15 · 2013: 10
- FWCI
- 5.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- acetylcholinesterase, HDAC4, histone deacetylase, stress, transcriptional memory, alternative splicing, H3K9 acetylation, H3K9 trimethylation, histone modifications, chromatin structure, sodium butyrate, hippocampus, cholinergic neurotransmission, long-term stress effects
- MeSH terms
- Acetylcholinesterase, Animals, Chromatin, Exons, Hippocampus, Histone Deacetylases, Male, Neurons, Promoter Regions, Genetic, Stress, Physiological, Swimming, Transcription, Genetic, DNA Methylation, Gene Silencing, Epigenesis, Genetic, Mice, Histone Deacetylase Inhibitors
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