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.
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24 July 2019
The original article inadvertently had a mistake in Fig.��3a and b. The authors regret to these errors.
24 July 2019
The original article inadvertently had a mistake in Fig.��3a and b. The authors regret to these errors.
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Acknowledgments
This work was supported by the Department of Biotechnology, Ministry of Science and Technology (BT/PR3996/MED/97/57/2011), Government of India. We also acknowledge the University Grants Commission, India, for senior research fellowship to S.S. and DBT-BHU Interdisciplinary School of Life Sciences, Banaras Hindu University, for the use of real-time PCR, cryotome, and confocal microscopy facility.
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Figure 1.
Diagrammatic representation of promoter regions of Arc, Egr1, Homer1 and Narp amplified by qPCR. The green region represents the promoter region amplified for MeDIP and ChIP qPCR assay. (TSS- Transcription start site). (GIF 1176 kb)
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Srivas, S., Thakur, M.K. Epigenetic regulation of neuronal immediate early genes is associated with decline in their expression and memory consolidation in scopolamine-induced amnesic mice. Mol Neurobiol 54, 5107–5119 (2017). https://doi.org/10.1007/s12035-016-0047-4
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DOI: https://doi.org/10.1007/s12035-016-0047-4