BDNF and NT-3 promote thalamocortical axon growth with distinct substrate and temporal dependency
BDNF and NT-3 promote thalamocortical axon growth with distinct substrate and temporal dependency
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DOI：
10.1111/j.1460-9568.2004.03228.x
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发表时间：
2004-03-01
影响因子：
3.4
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Hanamura, K;Harada, A;Yamamoto, N
将胚胎大鼠丘脑培养在胶原包被的底物或固定的皮质切片上，分别加入脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)，研究神经营养因子在丘脑轴突生长中的作用。BDNF和NT-3均促进轴突生长，但促进轴突生长的活性依赖于培养底物。BDNF可促进胶原膜上轴突的生长，而NT-3不能促进轴突生长。相反，NT-3可显著促进固定皮质上轴突的生长，但BDNF的作用不明显。对培养的丘脑细胞的半定量逆转录-聚合酶链式反应(RT-PCR)分析表明，培养底物不改变其受体TrkB和trkC的表达。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)染色进一步证实神经营养因子促进轴突生长不是由于减少细胞死亡。BDNF和NT-3水平的发育变化表明，与丘脑皮质轴突到达靶层后BDNF的快速升高相反，NT-3蛋白的调节伴随着它们在新皮质的生长阶段。提示BDNF和NT-3通过不同的底物依赖和发育阶段促进丘脑轴突生长。
The role of neurotrophins in thalamic axon growth was studied by culturing embryonic rat thalamus on collagen-coated substrate or fixed cortical slices in the presence of either brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3). Both BDNF and NT-3 promoted axonal growth, but the axonal growth-promoting activity depended on culture substrates. Axonal growth on collagen-coated membrane was accelerated by BDNF, but not by NT-3. In contrast, axonal outgrowth on fixed cortex was significantly enhanced by NT-3, but not by BDNF Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of cultured thalamic cells demonstrated that culture substrates did not alter the expression of their receptors, trkB and trkC. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining further demonstrated that axonal growth promoted by neurotrophins was not due to reduction of cell death. Measurement of the developmental changes in BDNF and NT-3 levels revealed that, in contrast to the rapid elevation of BDNF after the arrival of thalamocortical axons to their target layer, the regulation of NT-3 protein accompanies the phase of their outgrowth in neocortex. These findings suggest that BDNF and NT-3 promote thalamic axon growth in different manners in terms of substrate dependency and developmental stage.