Cited by 793Memory and Neural MechanismsEpigenetics and DNA MethylationNeuroscience and Neuropharmacology Research

Epigenetic Regulation of bdnf Gene Transcription in the Consolidation of Fear Memory

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Lubin, Farah D., Roth, Tania L., Sweatt, J. David·2008·The Journal of Neuroscience

Abstract

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.

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Crossref · 10.1523/jneurosci.1786-08.2008

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  • 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)

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Authors
Lubin, F. D., Roth, T. L., & Sweatt, J. D.
Affiliations
University of Alabama at Birmingham (US)
Venue
The Journal of Neuroscience
Published
2008-10-15
Volume
28
Issue
42
Pages
10576-10586
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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

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