title: Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex.
abstract: Epigenetic mechanisms have recently been known to play fundamental roles in the regulation of synaptic plasticity, and learning and memory tasks in many brain regions, such as the hippocampus, the amygdala, the insular cortex. However, epigenetic mechanism in the medial prefrontal cortex (mPFC), also a crucial neural locus for the control of cognition and emotion, is not well known. The present study investigated the epigenetic regulation of two genes, reelin and brain-derived neurotrophic factor (bdnf), both play important roles in neural plasticity, in the mPFC. The data showed that the levels of total DNA methyltransferase (DNMTs), total histone acetyltransferases (HATs), global acetylated histone 3 (H3) and global acetylated histone 4 (H4) were all changed with the induction of long-term potentiation (LTP) in the mPFC, implying that DNA methylation and histone acetylation may involve in synaptic plasticity in the mPFC. The present results further demonstrated that the demethylation status of reelin and bdnf, and acetylated H3 and acetylated H4 at the reelin and the bdnf promoters in the mPFC were enhanced by the delivery of LTP-inducing high-frequency stimulation (HFS). Consistently, infusion of DNMT inhibitor, 5-azacytidine (5-azaC), or histone deacetylases (HDACs) inhibitor, sodium butyrate (NaB), into the mPFC could interfere with LTP-associated demethylation and acetylation of reelin and bdnf genes, and the induction of LTP as well. Long-term retention of trace fear memory, which is dependent on mPFC function, was also altered by administration of these inhibitors into the mPFC. These findings suggest that epigenetic regulation of DNA demethylation and histone acetylation of target genes, such as reelin and bdnf, might underlie the mechanisms of synaptic plasticity and memory retention in the mPFC.
authors.affiliation: School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China. lsui@usst.edu.cn
authors.forename: Li
authors.initials: L
authors.lastname: Sui
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Ju
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology; D015254:DNA Modification Methylases / Q000032:analysis; D044127:Epigenesis, Genetic / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005239:Fear / Q000502:physiology; D051548:Histone Acetyltransferases / Q000032:analysis; D006657:Histones / Q000032:analysis; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D008568:Memory / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D006657:Histones; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D015254:DNA Modification Methylases; D051548:Histone Acetyltransferases; D012697:Serine Endopeptidases