title: Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice.
abstract: Recently, we reported a correlation of scopolamine mediated decline in memory consolidation with increase in the expression of DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) in the mouse hippocampus. Memory consolidation is a protein synthesis-dependent process which involves the expression of synaptic plasticity genes, particularly neuronal immediate early genes (IEGs). However, the mechanism of regulation of these genes during decline in memory is poorly understood. Therefore, we have studied the epigenetic regulation of expression of neuronal IEGs in scopolamine-induced amnesic mice. Scopolamine significantly impaired memory consolidation as tested by radial arm maze, and the expression of neuronal IEGs was downregulated in the hippocampus as revealed by qRT-PCR and Western blotting. Further, methylated DNA immunoprecipitation (MeDIP) analysis showed increase in DNA methylation, while chromatin immunoprecipitation (ChIP) revealed decrease in H3K9/14 acetylation at the promoter of neuronal IEGs. Taken together, the present study shows that increased DNA methylation and decreased histone acetylation at the promoter of neuronal IEGs are associated with decline in their expression and memory consolidation during scopolamine-induced amnesia. These findings suggest that the epigenetic regulation through altered DNA methylation and histone acetylation might be explored further to develop potential therapeutic interventions for amnesia.
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Institute of Sciences, Banaras Hindu University, Varanasi, 221 005, India.
authors.forename: Sweta
authors.initials: S
authors.lastname: Srivas
authors.affiliation: Biochemistry and Molecular Biology Laboratory, Brain Research Centre, Department of Zoology, Institute of Sciences, Banaras Hindu University, Varanasi, 221 005, India. mkt_bhu@yahoo.com.
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Thakur
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics*; D017781:Genes, Immediate-Early / Q000187:drug effects* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D000069077:Memory Consolidation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012601:Scopolamine / Q000494:pharmacology*
chemical_list: D012601:Scopolamine
keywords: Amnesia; DNA methylation; Epigenetics; Gene expression; Hippocampus; Histone acetylation