The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice
The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice
复制标题
TrkB 阳性多巴胺能神经元对成年 C57/BL 小鼠黑质中的 MPTP 损伤不太敏感
DOI：
10.1007/s11064-011-0491-5
复制
发表时间：
2011-10-01
影响因子：
4.4
通讯作者：
Chen, Liang-Wei
中科院分区：
文献类型：
--
作者：
Ding, Yin-Xiu;Xia, Yi;Chen, Liang-Wei
酪氨酸激酶受体TrkB和TrkC介导黑质-纹状体多巴胺能系统中脑源性神经营养因子（BDNF）和神经营养因子的神经保护作用，但它们在帕金森病时黑质损伤中的反应或表达变化尚不清楚。本研究应用免疫荧光、Fluoro-Jade染色和激光共聚焦显微镜技术，以对照组和1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）模型小鼠为对照，研究TrkB和TrkC在黑质多巴胺能神经元的分布和变化。结果显示，对照组大鼠黑质神经元的TrkB和TrkC免疫反应主要定位于细胞质和细胞膜。而酪氨酸羟化酶（TH）/TrkB或TH/TrkC双标记神经元在对照组黑质中大量分布，MPTP损伤后，它们明显下降，分别为正常水平的36.2-65.7%。在MPTP模型中，通过caspase-3和Fluoro-Jade染色证实黑质神经元的细胞凋亡或变性。更有趣的是，在MPTP模型中，TH/TrkB阳性神经元存活的细胞数比TH/TrkC阳性神经元存活的细胞数多。这项研究表明，含有TrkB的多巴胺神经元在MPTP小鼠模型的黑质中不太敏感，这表明Trks的特异性组织可能参与神经元对MPTP损伤的脆弱性，BDNF-TrkB信号转导可能在保护多巴胺神经元方面发挥更重要的作用，并表现出治疗帕金森病的潜力。
Tyrosine kinase receptors TrkB and TrkC mediate neuroprotective effects of the brain-derived neurotrophic factor (BDNF) and neurotrophins in the dopaminergic nigro-striatal system, but it is obscure about their responses or expression changes in the injured substantia nigra under Parkinson’s disease. In present study, immunofluorescence, Fluoro-Jade staining and laser scanning confocal microscopy were applied to investigate distribution and changes of TrkB and TrkC in the dopamine neurons of the substantia nigra by comparison of control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model. It revealed that TrkB and TrkC-immunoreactivities were substantially localized in cytoplasm and cell membrane of the substantia nigra neurons of control adults. While neurons double-labeled with tyrosine hydroxylase (TH)/TrkB, or TH/TrkC were distributed in a large numbers in the substantia nigra of controls, they apparently went down at 36.2–65.7% of normal level, respectively following MPTP insult. In MPTP model, cell apoptosis or degeneration of nigral neurons were confirmed by caspase-3 and Fluoro-Jade staining. More interestingly, TH/TrkB-positive neurons survived more in cell numbers in comparison with that of TH/TrkC-positive ones in the MPTP model. This study has indicated that TrkB-containing dopamine neurons are less sensitive in the substantia nigra of MPTP mouse model, suggesting that specific organization of Trks may be involved in neuronal vulnerability to MPTP insult, and BDNF-TrkB signaling may play more important role in protecting dopamine neurons and exhibit therapeutic potential for Parkinson’s disease.