title: Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression.
abstract: 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.
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Podda
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Cocco
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Mastrodonato
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Fusco
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Leone
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Saviana Antonella
authors.initials: SA
authors.lastname: Barbati
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.|Institute of Cell Biology and Neurobiology, CNR, Monterotondo, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Colussi
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ripoli
authors.affiliation: Institute of Human Physiology, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.|San Raffaele Pisana Scientific Institute for Research, Hospitalization and Health Care, 00163 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Grassi
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D044127:Epigenesis, Genetic; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D020813:Receptor, trkB / Q000378:metabolism; D065908:Transcranial Direct Current Stimulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D020813:Receptor, trkB