The effects of transcranial direct current stimulation (tDCS) on brain functions and the underlyingmolecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodaltDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effectswere associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoterI; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice alsoexhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBPon the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hinderedtDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggestthat anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatorysequences leading to increased expression of this gene, and support the therapeutic potential of tDCSfor brain diseases associated with impaired neuroplasticity.
Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression.
Barbati S A;
2016-01-01
Abstract
The effects of transcranial direct current stimulation (tDCS) on brain functions and the underlyingmolecular mechanisms are yet largely unknown. Here we report that mice subjected to 20-min anodaltDCS exhibited one-week lasting increases in hippocampal LTP, learning and memory. These effectswere associated with enhanced: i) acetylation of brain-derived neurotrophic factor (Bdnf) promoterI; ii) expression of Bdnf exons I and IX; iii) Bdnf protein levels. The hippocampi of stimulated mice alsoexhibited enhanced CREB phosphorylation, pCREB binding to Bdnf promoter I and recruitment of CBPon the same regulatory sequence. Inhibition of acetylation and blockade of TrkB receptors hinderedtDCS effects at molecular, electrophysiological and behavioral levels. Collectively, our findings suggestthat anodal tDCS increases hippocampal LTP and memory via chromatin remodeling of Bdnf regulatorysequences leading to increased expression of this gene, and support the therapeutic potential of tDCSfor brain diseases associated with impaired neuroplasticity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
