Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory
Open accessAbstract
Long-term memory formation requires selective changes in gene expression. Here, we determined the contribution of chromatin remodeling to learning-induced changes in brain-derived neurotrophic factor (bdnf) gene expression in the adult hippocampus. Contextual fear learning induced differential regulation of exon-specific bdnf mRNAs (I, IV, VI, IX) that was associated with changes in bdnf DNA methylation and altered local chromatin structure. Infusions of zebularine (a DNA methyltransferase inhibitor) significantly altered bdnf DNA methylation and triggered changes in exon-specific bdnf mRNA levels, indicating that altered DNA methylation is sufficient to drive differential bdnf transcript regulation in the hippocampus. In addition, NMDA receptor blockade prevented memory-associated alterations in bdnf DNA methylation, resulting in a block of altered bdnf gene expression in hippocampus and a deficit in memory formation. These results suggest epigenetic modification of the bdnf gene as a mechanism for isoform-specific gene readout during memory consolidation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Hypermethylation of BDNF promoter regions, especially exon IV, reduces BDNF expression.
“hypermethylation of BDNF promoter regions, especially exon IV, reduces BDNF expression”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [61]
The Discussion reports that decreased exon IV methylation accompanied increased exon IV transcripts and total bdnf mRNA in the hippocampus during fear-memory consolidation. The Results also link reduced exon IV methylation after DNMT inhibition with increased transcription. The broader claim that hypermethylation of BDNF promoter regions reduces expression is too categorical: the paper does not directly test induced hypermethylation, and methylation changes at other sites did not consistently change transcript levels. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566 · see citing works
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,949 · see citing works
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,497 · see citing works
Memory - A century of consolidation
McGaugh, J. L. (2000) · Science · doi:10.1126/science.287.5451.248 · Cited by 4,250 · see citing works
da Luz, A. C. D. D. S., Dias, G. P., Bevilaqua, M. C. D. N., Cocks, G. D., Gardino, P. F., Thuret, S., & Nardi, A. E. (2013) · Neuropsychobiology · doi:10.1159/000353269 · Cited by 4,012 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Nan, X., Ng, H.-H., Johnson, C. A., Laherty, C. D., Turner, B. M., Eisenman, R. N., & Bird, A. (1998) · Nature · doi:10.1038/30764 · Cited by 3,440 · see citing works
MethPrimer: designing primers for methylation PCRs
Li, L.-C., & Dahiya, R. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.11.1427 · Cited by 2,741 · see citing works
Epigenetics: A landscape takes shape
Goldberg, A. D., Allis, C. D., & Bernstein, E. (2007) · Cell · doi:10.1016/j.cell.2007.02.006 · Cited by 2,466 · see citing works
EUKARYOTIC CYTOSINE METHYLTRANSFERASES
Goll, M. G., & Bestor, T. H. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.010904.153721 · Cited by 2,066 · see citing works
Learning induces long-term potentiation in the hippocampus
Whitlock, J. R., Heynen, A. J., Shuler, M. G., & Bear, M. F. (2006) · Science · doi:10.1126/science.1128134 · Cited by 1,913 · see citing works
Ca2+ Influx Regulates BDNF Transcription by a CREB Family Transcription Factor-Dependent Mechanism
Tao, X., Finkbeiner, S., Arnold, D. B., Shaywitz, A. J., & Greenberg, M. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)81010-7 · Cited by 1,561 · see citing works
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405 · see citing works
Epigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400 · see citing works
Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90610-o · Cited by 1,371 · see citing works
Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2
Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., & Greenberg, M. E. (2003) · Science · doi:10.1126/science.1086446 · Cited by 1,232 · see citing works
Recovery of learning and memory is associated with chromatin remodelling
Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M., & Tsai, L.-H. (2007) · Nature · doi:10.1038/nature05772 · Cited by 1,227 · see citing works
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193 · see citing works
Covalent Modification of DNA Regulates Memory Formation
Miller, C. A., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.022 · Cited by 1,180 · see citing works
Self-citationRegulation 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
Self-citationMouse and rat <i>BDNF</i> gene structure and expression revisited
Aid, T., Kazantseva, A., Piirsoo, M., Palm, K., & Timmusk, T. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21139 · Cited by 943 · see citing works
Cyclical DNA methylation of a transcriptionally active promoter
Métivier, R., Gallais, R., Tiffoche, C., Péron, C. L., Jurkowska, R., Carmouche, R. P., Ibberson, D., Baráth, P., Demay, F., Reid, G., et al. (2008) · Nature · doi:10.1038/nature06544 · Cited by 942 · see citing works
Chromatin Acetylation, Memory, and LTP Are Impaired in CBP+/− Mice
Alarcón, J. M., Malleret, G., Touzani, K., Vronskaya, S., Ishii, S., Kandel, E. R., & Barco, A. (2004) · Neuron · doi:10.1016/j.neuron.2004.05.021 · Cited by 892 · see citing works
Zhou, Z., Hong, E. J., Cohen, S., Zhao, W.-N., Ho, H.-Y. H., Schmidt, L., Chen, W. G., Lin, Y., Savner, E., Griffith, E. C., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.037 · Cited by 877 · see citing works
CBP Histone Acetyltransferase Activity Is a Critical Component of Memory Consolidation
Korzus, E., Rosenfeld, M. G., & Mayford, M. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.002 · Cited by 823 · see citing works
Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum
Kumar, A., Choi, K.-H., Renthal, W., Tsankova, N. M., Theobald, D. E. H., Truong, H.-T., Russo, S. J., LaPlant, Q., Sasaki, T. S., Whistler, K. N., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.09.023 · Cited by 764 · see citing works
Identification of a Signaling Pathway Involved in Calcium Regulation of BDNF Expression
Shieh, P. B., Hu, S.-C., Bobb, K., Timmusk, T., & Ghosh, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)81011-9 · Cited by 693 · see citing works
Transient cyclical methylation of promoter DNA
Kangaspeska, S., Stride, B. D., Métivier, R., Polycarpou-Schwarz, M., Ibberson, D., Carmouche, R. P., Beneš, V., Gannon, F., & Reid, G. (2008) · Nature · doi:10.1038/nature06640 · Cited by 682 · see citing works
Rapid and selective induction of BDNF expression in the hippocampus during contextual learning
Hall, J., Thomas, K. L., & Everitt, B. (2000) · Nature Neuroscience · doi:10.1038/75698 · Cited by 669 · see citing works
DNA methylation and chromatin modification
Ng, H.-H., & Adrian, B. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80024-0 · Cited by 648 · see citing works
Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus
Levenson, J. M., Roth, T. L., Lubin, F. D., Miller, C. A., Huang, I.-C., Desai, P., Malone, L. M., & Sweatt, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511767200 · Cited by 615 · see citing works
Self-citationReelin promoter hypermethylation in schizophrenia
Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., Guidotti, A., & Costa, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503736102 · Cited by 553 · see citing works
BDNF in schizophrenia, depression and corresponding animal models
Angelucci, F., Brené, S., & Mathé, A. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001637 · Cited by 548 · see citing works
Brueckner, B., Boy, R. G., Siedlecki, P. S., Musch, T., Kliem, H., Zielenkiewicz, P., Suhai, S., Wießler, M., & Lyko, F. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2957 · Cited by 548 · see citing works
Bredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., & Barad, M. (2007) · Learning & Memory · doi:10.1101/lm.500907 · Cited by 548 · see citing works
Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia
Weickert, C. S., Hyde, T. M., Lipska, B. K., Herman, M. M., Weinberger, D. R., & Kleinman, J. E. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001308 · Cited by 533 · 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
Morris, R., Moser, E. I., Riedel, G., Martin, S. J., Sandin, J., Day, M., & O’Carroll, C. (2003) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2002.1264 · Cited by 480 · see citing works
Learning deficit in BDNF mutant mice.
Linnarsson, S., Björklund, A., & Ernfors, P. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01687.x · Cited by 471 · see citing works
Miller, C. A., Campbell, S. L., & Sweatt, J. D. (2007) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2007.07.016 · Cited by 417 · see citing works
Self-citationAbdolmaleky, H. M., Cheng, K., Russo, A. L., Smith, C. L., Faraone, S. V., Wilcox, M., Shafa, R., Glatt, S. J., Nguyen, G. H., Ponte, J. F., et al. (2005) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30140 · Cited by 390 · see citing works
ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning
Chwang, W. B., O’Riordan, K. J., Levenson, J. M., & Sweatt, J. D. (2006) · Learning & Memory · doi:10.1101/lm.152906 · Cited by 341 · see citing works
Self-citationRodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine
Liu, Q., Lü, L., Zhu, X.-G., Gong, J.-P., Shaham, Y., & Uhl, G. R. (2005) · Brain Research · doi:10.1016/j.brainres.2005.10.004 · Cited by 297 · see citing works
Nelson, E. D., Kavalali, E. T., & Monteggia, L. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3796-07.2008 · Cited by 254 · see citing works
The IκB Kinase Regulates Chromatin Structure during Reconsolidation of Conditioned Fear Memories
Lubin, F. D., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.039 · Cited by 234 · see citing works
Self-citationBrain-derived neurotrophic factor and control of synaptic consolidation in the adult brain
Soule, J. D., Messaoudi, E., & Bramham, C. R. (2006) · Biochemical Society Transactions · doi:10.1042/bst0340600 · Cited by 172 · see citing works
Identification of acis-Acting Dendritic Targeting Element in MAP2 mRNAs
Blichenberg, A., Schwanke, B., Rehbein, M., Garner, C. C., Richter, D., & Kindler, S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-20-08818.1999 · Cited by 171 · see citing works
Lauterborn, J. C., Rivera, S., Stinis, C., Hayes, V. Y., Isackson, P. J., & Gall, C. M. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-23-07428.1996 · Cited by 166 · see citing works
Rattiner, L. M., Davis, M. E., & Ressler, K. J. (2004) · Learning & Memory · doi:10.1101/lm.83304 · Cited by 136 · see citing works
Ou, L.-C., & Gean, P. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.034934 · Cited by 106 · see citing works
Ċastrén, E., Berzaghi, M. D. P., Lindholm, D., & Thoenen, H. (1993) · Experimental Neurology · doi:10.1006/exnr.1993.1124 · Cited by 101 · see citing works
Methylation Analysis of the Fragile X Syndrome by PCR
Das, S., Kubota, T., Song, M., DANIEL, R., Berry‐Kravis, E., Prior, T. W., Popovich, B. W., Rosser, L., Arinami, T., & Ledbetter, D. H. (1997) · Genetic Testing · doi:10.1089/gte.1997.1.151 · Cited by 57 · see citing works
Schirrmacher, E., Beck, C., Brueckner, B., et al. (2006) · Bioconjugate Chemistry · doi:10.1021/bc050300b · Cited by 46 · see citing works
Nanda, S. A., & Mack, K. J. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00242-3 · Cited by 33 · see citing works
Pal, R., Aǵbaş, A., Bao, X., Hui, D., Leary, C. B., Hunt, J., Naniwadekar, A. S., Michaelis, M. L., Kumar, K. N., & Michaelis, E. K. (2003) · Brain Research · doi:10.1016/j.brainres.2003.08.046 · Cited by 30 · see citing works
Aranda-Abreu, G. E., Hernández‐Aguilar, M. E., Soto, A., & Manzo, J. G. (2005) · Theoretical Biology and Medical Modelling · doi:10.1186/1742-4682-2-33 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906 · see citing works
Glutamate Receptor Ion Channels: Structure, Regulation, and Function
Traynelis, S. F., Wollmuth, L. P., McBain, C. J., Menniti, F. S., Vance, K. M., Ogden, K. K., Hansen, K. B., Yuan, H., Myers, S. J., & Dingledine, R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002451 · Cited by 3,568 · see citing works
TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661 · see citing works
Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00363 · Cited by 1,416 · see citing works
Lasting epigenetic influence of early-life adversity on the BDNF gene
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.028 · Cited by 1,273 · see citing works
Self-citationEpigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239 · see citing works
Potential therapeutic uses of BDNF in neurological and psychiatric disorders
Nagahara, A. H., & Tuszynski, M. H. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3366 · Cited by 867 · see citing works
Histone acetylation: molecular mnemonics on the chromatin
Gräff, J., & Tsai, L.-H. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3427 · Cited by 680 · see citing works
Neuronal activity modifies the DNA methylation landscape in the adult brain
Guo, J. U., Ma, D. K., Mo, H., Ball, M. P., Jang, M.-H., Bonaguidi, M. A., Balazer, J. A., Eaves, H. L., Xie, B., Ford, E., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2900 · Cited by 669 · see citing works
Davies, M. N., Volta, M., Pidsley, R., Lunnon, K., Dixit, A., Lovestone, S., Coarfa, C., Harris, R. A., Milosavljevic, A., Troakes, C., et al. (2012) · Genome Biology · doi:10.1186/gb-2012-13-6-r43 · Cited by 630 · see citing works
Epigenetics and the environmental regulation of the genome and its function
Zhang, T.-Y., & Meaney, M. J. (2010) · Annual Review of Psychology · doi:10.1146/annurev.psych.60.110707.163625 · Cited by 565 · see citing works
Epigenetic mechanisms in cognition
Day, J. J., & Sweatt, J. D. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.019 · Cited by 510 · see citing works
Self-citationDempster, E. L., Pidsley, R., Schalkwyk, L. C., Owens, S., Georgiades, A., Kane, F., Kalidindi, S., Picchioni, M., Kravariti, E., Toulopoulou, T., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr416 · Cited by 460 · see citing works
Epigenetic mechanisms in neurological disease
Jakovcevski, M., & Akbarian, S. (2012) · Nature Medicine · doi:10.1038/nm.2828 · Cited by 450 · see citing works
DNA methylation of BDNF as a biomarker of early-life adversity
Kundakovic, M., Gudsnuk, K., Herbstman, J. B., Tang, D., Perera, F. P., & Champagne, F. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408355111 · Cited by 426 · see citing works
Genetic and Epigenetic Networks in Intellectual Disabilities
van Bokhoven, H. (2011) · Annual Review of Genetics · doi:10.1146/annurev-genet-110410-132512 · Cited by 382 · see citing works
Epigenetic regulation of gene expression in physiological and pathological brain processes
Gräff, J., Kim, D., Dobbin, M. M., & Tsai, L.-H. (2011) · Physiological Reviews · doi:10.1152/physrev.00012.2010 · Cited by 373 · see citing works
Gomez‐Pinilla, F., Zhuang, Y., Feng, J., Ying, Z., & Fan, G. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07508.x · Cited by 367 · see citing works
Epigenetic influences on brain development and plasticity
Fagiolini, M., Jensen, C. L., & Champagne, F. A. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.009 · Cited by 362 · see citing works
Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene
Perroud, N., Salzmann, A., Prada, P., Nicastro, R., Hoeppli, M.-E., Furrer, S., Ardu, S., Krejci, I., Karege, F., & Malafosse, A. (2013) · Translational Psychiatry · doi:10.1038/tp.2012.140 · Cited by 320 · see citing works
The Emerging Field of Neuroepigenetics
Sweatt, J. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.023 · Cited by 324 · see citing works
Self-citationDevlin, A. M., Brain, U., Austin, J., & Oberlander, T. F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0012201 · Cited by 308 · see citing works
Epigenetic Regulation of the BDNF Gene: Implications for Psychiatric Disorders
Boulle, F., van den Hove, D. L. A., Jakob, S. B., Rutten, B. P., Hamon, M., van Os, J., Lesch, K.-P., Lanfumey, L., Steinbusch, H. W., & Kenis, G. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.107 · Cited by 282 · see citing works
Unternaehrer, E., Luers, P., Mill, J., Dempster, E., Meyer, A. H., Staehli, S., Lieb, R., Hellhammer, D. H., & Meinlschmidt, G. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.77 · Cited by 250 · see citing works
Roth, T. L., & David Sweatt, J. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02282.x · Cited by 246 · see citing works
Self-citationThe Role of Iron in Learning and Memory
Fretham, S. J. B., Carlson, E. S., & Georgieff, M. K. (2011) · Advances in Nutrition · doi:10.3945/an.110.000190 · Cited by 235 · see citing works
Suri, D., Veenit, V., Sarkar, A., Thiagarajan, D., Kumar, A., Nestler, E. J., Galande, S., & Vaidya, V. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.023 · Cited by 208 · see citing works
Stress and trauma: BDNF control of dendritic-spine formation and regression
Bennett, M. R., & Lagopoulos, J. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.005 · Cited by 199 · see citing works
Role of BDNF epigenetics in activity-dependent neuronal plasticity
Karpova, N. N. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.002 · Cited by 200 · see citing works
Epigenetic marking of the BDNF gene by early-life adverse experiences
Roth, T. L., & Sweatt, J. D. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.05.005 · Cited by 196 · see citing works
Self-citationWei, Y. B., Melas, P. A., Wegener, G., Mathe, A. A., & Lavebratt, C. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu032 · Cited by 186 · see citing works
Early life nutrition and neural plasticity
Georgieff, M. K., Brunette, K. E., & Tran, P. V. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000061 · Cited by 177 · see citing works
DNA methylation of the BDNF gene and its relevance to psychiatric disorders
Ikegame, T., Bundo, M., Murata, Y., Kasai, K., Kato, T., & Iwamoto, K. (2013) · Journal of Human Genetics · doi:10.1038/jhg.2013.65 · Cited by 179 · see citing works
Histone H2A.Z subunit exchange controls consolidation of recent and remote memory
Zovkic, I. B., Paulukaitis, B. S., Day, J. J., Etikala, D. M., & Sweatt, J. D. (2014) · Nature · doi:10.1038/nature13707 · Cited by 179 · see citing works
Self-citationEpigenetics and the Biological Basis of Gene × Environment Interactions
Bagot, R. C., & Meaney, M. J. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.06.001 · Cited by 177 · see citing works
Boersma, G. J., Lee, R. S., Cordner, Z. A., Ewald, E. R., Purcell, R. H., Moghadam, A. A., & Tamashiro, K. L. (2014) · Epigenetics · doi:10.4161/epi.27558 · Cited by 172 · see citing works
A Positive Autoregulatory BDNF Feedback Loop via C/EBPβ Mediates Hippocampal Memory Consolidation
Bambah-Mukku, D., Travaglia, A., Chen, D. Y., Pollonini, G., & Alberini, C. M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0324-14.2014 · Cited by 145 · see citing works
Epigenetic programming of the HPA axis: Early life decides
Murgatroyd, C., & Spengler, D. (2011) · Stress · doi:10.3109/10253890.2011.602146 · Cited by 138 · see citing works
Regulation of chromatin structure in memory formation
Roth, T. L., & Sweatt, J. D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.011 · Cited by 138 · see citing works
Self-citationEpigenetic mechanisms underlying learning and the inheritance of learned behaviors
Dias, B. G., Maddox, S. A., Klengel, T., & Ressler, K. J. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2014.12.003 · Cited by 125 · see citing works
Blaze, J., Scheuing, L., & Roth, T. L. (2013) · Developmental Neuroscience · doi:10.1159/000350716 · Cited by 123 · see citing works
Self-citationSakharkar, A. J., Vetreno, R. P., Zhang, H., Kokare, D. M., Crews, F. T., & Pandey, S. C. (2016) · Brain Structure and Function · doi:10.1007/s00429-016-1196-y · Cited by 122 · see citing works
DNA methylation regulates neuronal glutamatergic synaptic scaling
Meadows, J. P., Guzman-Karlsson, M. C., Phillips, S., Holleman, C., Posey, J. L., Day, J. J., Hablitz, J. J., & Sweatt, J. D. (2015) · Science Signaling · doi:10.1126/scisignal.aab0715 · Cited by 111 · see citing works
Self-citationChampagne, F. A. (2010) · Perspectives on Psychological Science · doi:10.1177/1745691610383494 · Cited by 110 · see citing works
Epigenetic memory: The Lamarckian brain
Fischer, A. (2014) · The EMBO Journal · doi:10.1002/embj.201387637 · Cited by 107 · see citing works
Complex epigenetic regulation of Engrailed-2 (EN-2) homeobox gene in the autism cerebellum
James, S. J., Shpyleva, S., Melnyk, S., Pavliv, O., & Pogribny, I. P. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.8 · Cited by 100 · see citing works
St-Cyr, S., & McGowan, P. O. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00145 · Cited by 102 · see citing works
Bartlett, A. A., Singh, R., & Hunter, R. G. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-53889-1_8 · Cited by 91 · see citing works
Epigenetic mechanisms in fear conditioning: Implications for treating post-traumatic stress disorder
Kwapis, J. L., & Wood, M. A. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.08.005 · Cited by 87 · see citing works
BDNF genetic variants and methylation: effects on cognition in major depressive disorder
Ferrer, A., Labad, J., Salvat-Pujol, N., Barrachina, M., Costas, J., Urretavizcaya, M., de Arriba-Arnau, A., Crespo, J. M., Soriano-Mas, C., Carracedo, Á., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0601-8 · Cited by 84 · see citing works
Environmental regulation of the neural epigenome
Caldji, C., Hellstrom, I. C., Zhang, T.-Y., Diorio, J., & Meaney, M. J. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.032 · Cited by 82 · see citing works
Kim, T. Y., Kim, S. J., Chung, H. G., Choi, J. H., Kim, S. H., & Kang, J. I. (2017) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12675 · Cited by 76 · see citing works
Cardenas-Aguayo, M. D. C., Kazim, S. F., Grundke-Iqbal, I., & Iqbal, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0053596 · Cited by 73 · see citing works
Molecular and cellular aspects of age-related cognitive decline and Alzheimer’s disease
Hullinger, R., & Puglielli, L. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.008 · Cited by 68 · see citing works
Longitudinal associations between BDNF promoter methylation and late-life depression
Kang, H.-J., Kim, J.-M., Bae, K.-Y., Kim, S.-W., Shin, I.-S., Kim, H.-R., Shin, M.-G., & Yoon, J.-S. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.12.035 · Cited by 65 · see citing works
Blaze, J., Asok, A., & Roth, T. L. (2015) · Stress · doi:10.3109/10253890.2015.1071790 · Cited by 52 · see citing works
Self-citationBDNF Methylation and Maternal Brain Activity in a Violence-Related Sample
Moser, D. A., Paoloni-Giacobino, A., Stenz, L., Adouan, W., Manini, A., Suardi, F., Cordero, M. I., Vital, M., Sancho Rossignol, A., Rusconi-Serpa, S., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0143427 · Cited by 51 · see citing works
DNA Methylation in the Developing Hippocampus and Amygdala of Anxiety-Prone versus Risk-Taking Rats
Simmons, R. K., Howard, J. L., Simpson, D. N., Akil, H., & Clinton, S. M. (2012) · Developmental Neuroscience · doi:10.1159/000336641 · Cited by 48 · see citing works
Caregiver maltreatment causes altered neuronal DNA methylation in female rodents
Blaze, J., & Roth, T. L. (2017) · Development and Psychopathology · doi:10.1017/s0954579417000128 · Cited by 48 · see citing works
Self-citationMaurel, O. M., Torrisi, S. A., Barbagallo, C., Purrello, M., Salomone, S., Drago, F., Ragusa, M., & Leggio, G. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105157 · Cited by 44 · see citing works
Ribeiro, A. C. R., Jahr, F. M., Hawkins, E., Kronfol, M. M., Younis, R. M., McClay, J. L., & Deshpande, L. S. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119765 · Cited by 30 · see citing works
Scott, H., Smith, A. E., Barker, G. R., Uney, J. B., & Warburton, E. C. (2017) · Neuroepigenetics · doi:10.1016/j.nepig.2017.02.001 · Cited by 18 · see citing works
Ahmed, O. G., Shehata, G. A., Ali, R. M., Makboul, R., Abd Allah, E. S. H., & Abd el-Rady, N. M. (2021) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2020-0923 · Cited by 14 · see citing works
Montel Hayes, R., Mason, C. E., & Miller, J. J. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1671122 · Cited by 5 · see citing works
“For example, exon IV of BDNF is highly sensitive to environmental signals and hypermethylation of BDNF promoter regions, especially exon IV, reduces BDNF expression (61).”
- Authors
- Lubin, F. D., Roth, T. L., & Sweatt, J. D.
- Affiliations
- University of Alabama at Birmingham (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-10-15
- Volume
- 28
- Issue
- 42
- Pages
- 10576-10586
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3312036
- OpenAlex
- W2092765329
- Cited by
- 793
- References
- 58
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 24 · 2023: 22 · 2022: 35 · 2021: 39 · 2020: 31 · 2019: 46 · 2018: 37 · 2017: 54 · 2016: 64 · 2015: 55 · 2014: 75 · 2013: 86 · 2012: 57
- FWCI
- 23.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brain Research Foundation
- Epilepsy Foundation
- McKnight Foundation
- Evelyn F. McKnight Brain Research Foundation
- National Alliance for Research on Schizophrenia and Depression
- Coins for Alzheimer's Research Trust
- Alzheimer's Research Trust
- National Institutes of Health (MH082106, NS37444)
- National Institute of Mental Health (K99MH082106, R00MH082106, MH 57014, R01MH057014, MH08106)
- National Institute of Neurological Disorders and Stroke (NS 37444, R01NS013546, NS013546, NS04811, F32NS048811, P01NS037444)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain-derived neurotrophic factor, epigenetic regulation, DNA methylation, chromatin remodeling, fear memory consolidation, hippocampus, zebularine, NMDA receptor, long-term memory formation, gene expression regulation
- MeSH terms
- Animals, Base Sequence, Fear, Male, Memory, Molecular Sequence Data, Transcription, Genetic, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Protein Isoforms, Epigenesis, Genetic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review