Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression

• Published in: Scientific reports Vol. 6; no. 1; p. 22180
• Main Authors: Podda, Maria Vittoria, Cocco, Sara, Mastrodonato, Alessia, Fusco, Salvatore, Leone, Lucia, Barbati, Saviana Antonella, Colussi, Claudia, Ripoli, Cristian, Grassi, Claudio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.02.2016; Nature Publishing Group
• Subjects: 13/1; 38/15; 38/77; 631/378/2584/1695; 631/378/87; 64/60; 9/74; Acetylation; Animals; Behavioral plasticity; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - metabolism; Chromatin Assembly and Disassembly; Chromatin remodeling; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - metabolism; Electrical stimulation of the brain; Epigenesis, Genetic; ESB; Exons; Hippocampal plasticity; Hippocampus; Hippocampus - metabolism; Hippocampus - physiology; Humanities and Social Sciences; Kinases; Learning; Long-Term Potentiation; Male; Memory; Mice; Mice, Inbred C57BL; Molecular modelling; multidisciplinary; Neuroplasticity; Phosphorylation; Receptor, trkB - metabolism; Regulatory sequences; Rodents; Science; Synaptic plasticity; Transcranial Direct Current Stimulation; TrkB receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22180

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.