Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration
Axonal protection by brain-derived neurotrophic factor associated with CREB phosphorylation in tumor necrosis factor-α-induced optic nerve degeneration
复制标题
DOI：
10.1007/s00401-008-0440-9
复制
发表时间：
2009-01-01
影响因子：
12.7
通讯作者：
Ueno, Satoki
中科院分区：
文献类型：
--
作者：
Fujino, Hiromi;Kitaoka, Yasushi;Ueno, Satoki
脑源性神经营养因子（BDNF）是一种有效的生存和发育因子，受环腺苷酸反应元件结合蛋白（CREB）调节，对视网膜神经节细胞（RGC）死亡具有保护作用。然而，BDNF对视神经轴突变性的影响仍有待研究。在这项研究中，我们表明，玻璃体内注射肿瘤坏死因子（TNF）-α诱导瞬时增加磷酸化CREB（p-CREB）和BDNF的表达在视神经。外源性BDNF的施用进一步增加了p-CREB和内源性BDNF水平，并对TNF-α诱导的轴突损失产生神经保护作用。CRE诱饵寡核苷酸可显著抑制TNF-α诱导的BDNF mRNA和蛋白的增加。外源性BDNF对轴突的保护作用也被CRE诱饵寡核苷酸抑制。这些结果表明，外源性BDNF的保护作用可能与CREB磷酸化和内源性BDNF在视神经中的增加有关。
Brain-derived neurotrophic factor (BDNF) is a potent survival and developmental factor that is regulated by cyclic AMP-response element binding protein (CREB) and has a protective effect against retinal ganglion cell (RGC) death. However, the effect of BDNF on the optic nerve axonal degeneration remains to be examined. In this study, we show that intravitreal injection of tumor necrosis factor (TNF)-alpha induces transient increases in phosphorylated-CREB (p-CREB) and BDNF expression in the optic nerve. Administration of exogenous BDNF further increased the p-CREB and endogenous BDNF level and exerted a neuroprotective effect against TNF-alpha-induced axonal loss. The increases in BDNF mRNA and protein induced by TNF-alpha were inhibited significantly by a CRE decoy oligonucleotide. The protective effect of exogenous BDNF on axons was also inhibited by the CRE decoy oligonucleotide. These results suggest that the protective effect of exogenous BDNF may be associated with increases in CREB phosphorylation and endogenous BDNF in the optic nerve.