Intensive Rehabilitation Enhances Lymphocyte BDNF-TrkB Signaling in Patients With Parkinson's Disease.
Intensive Rehabilitation Enhances Lymphocyte BDNF-TrkB Signaling in Patients With Parkinson's Disease.
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DOI：
10.1177/1545968315600272
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发表时间：
2016-06
影响因子：
4.2
通讯作者：
Ghilardi MF
中科院分区：
文献类型：
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作者：
Fontanesi C;Kvint S;Frazzitta G;Bera R;Ferrazzoli D;Di Rocco A;Rebholz H;Friedman E;Pezzoli G;Quartarone A;Wang HY;Ghilardi MF
在一项动物和人类联合研究中，我们之前发现，增强皮质可塑性的五天治疗还可以促进脑源性神经营养因子 (BDNF)-酪氨酸受体激酶 B (TrkB) 信号传导，并增加皮质和外周淋巴细胞中激活的 TrkB 和 N-甲基-D-天冬氨酸受体 (NMDAR) 的关联。电生理学和行为研究表明，帕金森病 (PD) 患者的皮质可塑性普遍下降。在这里，我们测试了这样一个假设：改善运动功能并似乎减缓症状进展的运动计划可以增强淋巴细胞中的 BDNF-TrkB 信号传导。 16 名 PD 患者接受了为期 4 周的多学科强化康复治疗 (MIRT)，其中包括有氧训练、物理治疗和职业治疗。在 MIRT 两周和四周之前、之后收集血液。分离淋巴细胞以检查与重组人 BDNF 孵育诱导的 BDNF-TrkB 信号传导。对 TrkB 信号复合物、细胞外信号调节激酶 2 和蛋白激酶 B 进行免疫沉淀；通过蛋白质印迹法测定免疫复合物的含量。 MIRT 后，所有患者的运动功能均有所改善。 TrkB 与 NMDAR 和 BDNF-TrkB 信号传导的相互作用在外周淋巴细胞的受体、细胞内介质和下游水平上增加。 UPDRSII 和总分的下降与受体、细胞内介质和 NMDAR 相互作用水平的 TrkB 信号传导的增加显着相关。 UPDRS 评分降低与淋巴细胞活性变化之间的显着相关性表明淋巴细胞中 BDNF-TrkB 信号传导增强与 PD 症状严重程度减轻可能相关。
In a combined animal and human study, we have previously found that a five-day treatment that enhances cortical plasticity also facilitates brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB) signaling and increases activated TrkB and N-methyl-D-aspartate receptor (NMDAR) association in both the cortex and the peripheral lymphocytes. Patients with Parkinson’s disease (PD) in general show decreased cortical plasticity, as demonstrated by electrophysiological and behavioral studies. Here we test the hypothesis that an exercise program that improves motor function and seems to slow down symptoms’ progression can enhance BDNF-TrkB signaling in lymphocytes. Sixteen patients with PD underwent a four-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT), which included aerobic training, physical and occupational therapy. Blood was collected before, after two- and four-week MIRT. Lymphocytes were isolated to examine BDNF-TrkB signaling induced by incubation with recombinant human BDNF. TrkB signaling complexes, extracellular-signal-regulated kinase-2 and protein-kinase-B were immunoprecipitated; content of immunocomplexes was determined by Western blotting. After MIRT, all patients showed improvement in motor function. TrkB interaction with NMDAR and BDNF-TrkB signaling increased in peripheral lymphocytes at receptor, intracellular mediators and downstream levels. The decrements in UPDRSII and total scores were significantly correlated with the increases in TrkB signaling at receptor, intracellular mediators and NMDAR interaction levels. The significant correlation between reduced UPDRS scores and the changes in lymphocytes’ activity suggest that enhanced BDNF-TrkB signaling in lymphocyte and reduced severity of PD symptoms may be related.