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.
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.
重复经颅磁刺激（rTMS）可诱导神经元长时程增强或抑制。尽管脑源性神经营养因子（BDNF）及其同源酪氨酸受体激酶 B（TrkB）有助于 rTMS 的作用，但它们的确切作用和潜在机制仍知之甚少。在这里，我们发现每天进行 5 赫兹 rTMS 刺激 5 天，可通过增加 BDNF 与 TrkB 的亲和力来改善大鼠的 BDNF-TrkB 信号，从而导致更高的酪氨酸磷酸化 TrkB、更多的 PLC-γ1 和 shc/N-shc 募集到 TrkB，以及更高的下游 ERK2 和 PI-3K 活性在额皮质和淋巴细胞中。升高的 BDNF-TrkB 信号伴随着激活的 TrkB 和 NMDA 受体（NMDAR）之间的关联增加。在正常的人类受试者中，对运动皮质进行 5 天 rTMS 可降低静息运动阈值，这与淋巴细胞中 BDNF-TrkB 信号的增强和 TrkB-NMDAR 关联的增强相关。这些发现表明，皮质 rTMS 可促进皮质和淋巴细胞中 BDNF-TrkB-NMDAR 的功能。
