Repetitive transcranial magnetic stimulation induces long-lasting changes in protein expression and histone acetylation

Sci Rep. 2015 Nov 20;5:16873. doi: 10.1038/srep16873.


The use of non-invasive brain stimulation like repetitive transcranial magnetic stimulation (rTMS) is an increasingly popular set of methods with promising results for the treatment of neurological and psychiatric disorders. Despite great enthusiasm, the impact of non-invasive brain stimulation on its neuronal substrates remains largely unknown. Here we show that rTMS applied over the frontal cortex of awaken mice induces dopamine D2 receptor dependent persistent changes of CDK5 and PSD-95 protein levels specifically within the stimulated brain area. Importantly, these modifications were associated with changes of histone acetylation at the promoter of these genes and prevented by administration of the histone deacetylase inhibitor MS-275. These findings show that, like several other psychoactive treatments, repeated rTMS sessions can exert long-lasting effects on neuronal substrates. This underscores the need of understanding these effects in the development of future clinical applications as well as in the establishment of improved guidelines to use rTMS in non-medical settings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Benzamides / pharmacology
  • Blotting, Western
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase 5 / metabolism*
  • Disks Large Homolog 4 Protein
  • Epigenesis, Genetic / drug effects
  • Female
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • Histone Deacetylase Inhibitors / pharmacology
  • Histones / metabolism*
  • Immunohistochemistry
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Promoter Regions, Genetic / genetics
  • Pyridines / pharmacology
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism*
  • Time Factors
  • Transcranial Magnetic Stimulation / methods*
  • Wakefulness


  • Benzamides
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Histone Deacetylase Inhibitors
  • Histones
  • Membrane Proteins
  • Pyridines
  • Receptors, Dopamine D2
  • entinostat
  • Cyclin-Dependent Kinase 5
  • Cdk5 protein, mouse
  • Guanylate Kinases