EPIGENETIC REGULATION OF BDNF GENE TRANSCRIPTION IN THE CONSOLIDATION OF FEAR MEMORY
By F. Lubin, T. Roth, J. Sweatt. Journal of Neuroscience, 2008
806 citations recorded by the source corpus.
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.
Subfields: Developmental Neuroscience, Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/b648fca9be2a48fac97bb320204ef32fd4b667ad
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Citations in the corpus
- Potential therapeutic uses of BDNF in neurological and psychiatric disorders (2011, background): “Fear-conditioning can also differentially regulate the expression of Bdnf mRNAs at specific exons following Bdnf DNA methylatio”
- Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood (2012, background): “Epigenetic processes control several neurobiological and cognitive processes, including neurogenesis and brain development [2], neuronal activity [3], learning and memory [4], drug addiction [5], neurodegeneration [6], and circadian rhythm [7].”
- Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “It also should be noted that NMDA, AMPA, and kainate receptors are key mediators of signal transduction events that convert environmental stimuli into genetic changes through regulation of gene transcription and epigenetic chromatin remodeling in neural cells, an area of emerging interest (Carrasco ”
- Epigenetics and the biological definition of gene x environment interactions. (2010, background): “Indeed, Lubin et al. (2008) provided evidence for an alteration of the methylation state of the same bdnf promoter following contextual fear conditioning in adult rats (also see Bredy et al., 2007).”
- Brain-Derived Neurotrophic Factor: A Key Molecule for Memory in the Healthy and the Pathological Brain (2019, background): “Additionally, the expression of specific BDNF exons can be regulated by epigenetic mechanisms (Lubin et al., 2008), suggesting that environmental experiences dynamically influence mature BDNF levels.”
- DNA Methylation and Its Basic Function (2013, background): “When neuronal activity is inhibited during fear conditioning , not only is memory formation prevented but so are changes in DNA methylation (Lubin et al, 2008).”