title: Repetitive transcranial magnetic stimulation enhances BDNF-TrkB signaling in both brain and lymphocyte.
abstract: 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.
authors.affiliation: Department of Physiology, Pharmacology & Neuroscience, Sophie Davis School of Biomedical Education, The City University of New York Medical School, New York, New York 10031, USA. hywang@sci.ccny.cuny.edu
authors.forename: Hoau-Yan
authors.initials: HY
authors.lastname: Wang
authors.forename: Domenica
authors.initials: D
authors.lastname: Crupi
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.forename: Andres
authors.initials: A
authors.lastname: Stucky
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cruciata
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Rocco
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.forename: M Felice
authors.initials: MF
authors.lastname: Ghilardi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000528:radiation effects*; D019208:Brain-Derived Neurotrophic Factor / Q000134:cerebrospinal fluid*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D018482:Muscle, Skeletal / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000134:cerebrospinal fluid*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology / Q000528:radiation effects*; D013223:Statistics as Topic; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016194:Receptors, N-Methyl-D-Aspartate; D020813:Receptor, trkB