PMID- 26908001 OWN - NLM STAT- MEDLINE DCOM- 20170313 LR - 20220321 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 6 DP - 2016 Feb 24 TI - Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression. PG - 22180 LID - 10.1038/srep22180 [doi] LID - 22180 AB - The effects of transcranial direct current stimulation (tDCS) on brain functions and the underlying molecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodal tDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effects were associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoter I; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice also exhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBP on the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hindered tDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggest that anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatory sequences leading to increased expression of this gene, and support the therapeutic potential of tDCS for brain diseases associated with impaired neuroplasticity. FAU - Podda, Maria Vittoria AU - Podda MV AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Cocco, Sara AU - Cocco S AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Mastrodonato, Alessia AU - Mastrodonato A AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Fusco, Salvatore AU - Fusco S AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Leone, Lucia AU - Leone L AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Barbati, Saviana Antonella AU - Barbati SA AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Colussi, Claudia AU - Colussi C AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. AD - Institute of Cell Biology and Neurobiology, CNR, Monterotondo, Italy. FAU - Ripoli, Cristian AU - Ripoli C AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. FAU - Grassi, Claudio AU - Grassi C AD - Institute of Human Physiology, Universita Cattolica, Largo F. Vito 1, 00168 Rome, Italy. AD - San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160224 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Chromatin Assembly and Disassembly MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - *Epigenesis, Genetic MH - Hippocampus/metabolism/physiology MH - *Long-Term Potentiation MH - Male MH - *Memory MH - Mice MH - Mice, Inbred C57BL MH - Receptor, trkB/metabolism MH - *Transcranial Direct Current Stimulation PMC - PMC4764914 EDAT- 2016/02/26 06:00 MHDA- 2017/03/14 06:00 PMCR- 2016/02/24 CRDT- 2016/02/25 06:00 PHST- 2015/10/27 00:00 [received] PHST- 2016/02/09 00:00 [accepted] PHST- 2016/02/25 06:00 [entrez] PHST- 2016/02/26 06:00 [pubmed] PHST- 2017/03/14 06:00 [medline] PHST- 2016/02/24 00:00 [pmc-release] AID - srep22180 [pii] AID - 10.1038/srep22180 [doi] PST - epublish SO - Sci Rep. 2016 Feb 24;6:22180. doi: 10.1038/srep22180.