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 days improves BDNF-TrkB signaling in rats by increasing the affinity of BDNF for TrkB that 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 N-methyl-D-aspartate receptor (NMDAR). In normal human subjects, 5-day rTMS to motor cortex decreased resting motor threshold that 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.

Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder

“…In addition, there are several other biological aspects that should be considered to understand the mechanism of rTMS, including various aspects of stress biology, immune function disruptions, neural structure, and function, as well as circadian rhythms [42]. Some animal studies also suggest that rTMS affects neurotransmitter systems of glutamate and gamma-aminobutyric acid (GABA); stress-induced activity of the hypothalamic-pituitaryadrenal (HPA) system; and neurotrophic signaling factors, such as brain derived neurotrophic factor (BDNF) [43,44,45]. High-frequency rTMS has been reported to regulate brain activity and increase cortical excitability [46].…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…The reduced plasticity exhibited in chronic injuries and aged patients may make functional integration difficult, even if combined with rehabilitation. Direct brain stimulation with TMS has been used to stimulate brain regions for stroke recovery (Takeuchi et al, 2005;Khedr et al, 2010) and enhance BDNF-mediated plasticity (Wang et al, 2011a). TMS has also been shown to increase the proliferation of resident adult NSCs in the SVZ though the miR-25/p57 pathway (Guo et al, 2014a).…”

Rapid Relief of Treatment Resistant Depression by Facilitated Ketamine Infusion: A Preliminary Report

“…Hence, the primary goal of the present study is to identify a therapy that will provide a greater likelihood of lasting successful results than has been achieved with ketamine or TMS along, while hopefully reducing the undesirable adverse effects of the conventional pharmacopoeia (Cazzoli et al, 2012;Gersner et al, 2011;Wang et al, 2011). …”