Repetitive transcranial magnetic stimulation enhances BDNF-TrkB signaling in both brain and lymphocyte

J Neurosci. 2011 Jul 27;31(30):11044-54. doi: 10.1523/JNEUROSCI.2125-11.2011.


Repetitive transcranial magnetic stimulation (rTMS) induces neuronal long-term potentiation or depression. Although brain-derived neurotrophic factor (BDNF) and its cognate tyrosine receptor kinase B (TrkB) contribute to the effects of rTMS, their precise role and underlying mechanism remain poorly understood. Here we show that daily 5 Hz rTMS for 5 d improves BDNF-TrkB signaling in rats by increasing the affinity of BDNF for TrkB, which results in higher tyrosine-phosphorylated TrkB, increased recruitment of PLC-γ1 and shc/N-shc to TrkB, and heightened downstream ERK2 and PI-3K activities in prefrontal cortex and in lymphocytes. The elevated BDNF-TrkB signaling is accompanied by an increased association between the activated TrkB and NMDA receptor (NMDAR). In normal human subjects, 5 d rTMS to motor cortex decreased resting motor threshold, which correlates with heightened BDNF-TrkB signaling and intensified TrkB-NMDAR association in lymphocytes. These findings suggest that rTMS to cortex facilitates BDNF-TrkB-NMDAR functioning in both cortex and lymphocytes.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Animals
  • Brain / metabolism
  • Brain / radiation effects*
  • Brain-Derived Neurotrophic Factor / cerebrospinal fluid*
  • Cross-Over Studies
  • Double-Blind Method
  • Electromyography
  • Evoked Potentials, Motor / physiology
  • Female
  • Gene Expression Regulation / physiology
  • Gene Expression Regulation / radiation effects*
  • Humans
  • In Vitro Techniques
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects*
  • Male
  • Muscle, Skeletal / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / cerebrospinal fluid*
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Signal Transduction / physiology
  • Signal Transduction / radiation effects*
  • Statistics as Topic
  • Transcranial Magnetic Stimulation*
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • Receptors, N-Methyl-D-Aspartate
  • Receptor, trkB