Inhibition of DNA Methylation Impairs Synaptic Plasticity during an Early Time Window in Rats
Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, m...
| Veröffentlicht in: | Neural plasticity. - 1998. - 2016(2016) vom: 06., Seite 4783836 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2016
|
| Zugriff auf das übergeordnete Werk: | Neural plasticity |
| Schlagworte: | Journal Article Enzyme Inhibitors Mecp2 protein, rat Methyl-CpG-Binding Protein 2 Decitabine 776B62CQ27 Azacitidine M801H13NRU |
| Zusammenfassung: | Although the importance of DNA methylation-dependent gene expression to neuronal plasticity is well established, the dynamics of methylation and demethylation during the induction and expression of synaptic plasticity have not been explored. Here, we combined electrophysiological, pharmacological, molecular, and immunohistochemical approaches to examine the contribution of DNA methylation and the phosphorylation of Methyl-CpG-binding protein 2 (MeCP2) to synaptic plasticity. We found that, at twenty minutes after theta burst stimulation (TBS), the DNA methylation inhibitor 5-aza-2-deoxycytidine (5AZA) impaired hippocampal long-term potentiation (LTP). Surprisingly, after two hours of TBS, when LTP had become a transcription-dependent process, 5AZA treatment had no effect. By comparing these results to those in naive slices, we found that, at two hours after TBS, an intergenic region of the RLN gene was hypomethylated and that the phosphorylation of residue S80 of MeCP2 was decreased, while the phosphorylation of residue S421 was increased. As expected, 5AZA affected only the methylation of the RLN gene and exerted no effect on MeCP2 phosphorylation patterns. In summary, our data suggest that tetanic stimulation induces critical changes in synaptic plasticity that affects both DNA methylation and the phosphorylation of MeCP2. These data also suggest that early alterations in DNA methylation are sufficient to impair the full expression of LTP |
|---|---|
| Beschreibung: | Date Completed 29.08.2017 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1687-5443 |
| DOI: | 10.1155/2016/4783836 |