胶质细胞系源性神经营养因子诱导形成血脑屏障的内皮细胞的屏障功能。

Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier.

作者信息

Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, Furuuchi K, Kokai Y, Nakagawa T, Mori M, Sawada N

机构信息

Department of Pathology, Department of Ophthalmology, Department of Neurosurgery, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, 060, Japan.

出版信息

Biochem Biophys Res Commun. 1999 Jul 22;261(1):108-12. doi: 10.1006/bbrc.1999.0992.

DOI:10.1006/bbrc.1999.0992

PMID:10405331

Abstract

Since a deep involvement of astrocytes, a kind of glial cells, in differentiation of the blood-brain barrier (BBB) has been suggested, we examined the relation of glial cell line-derived neurotrophic factor (GDNF) to the BBB. First, immunohistochemical examination of the cerebral cortex of rats revealed that glial cell line-derived neurotrophic factor receptor (GFRalpha1) was preferentially expressed on the cell membranes of capillary endothelial cells. Second, to elucidate the effects of GDNF on the BBB, capillary endothelial cells isolated from the porcine cerebral cortex were cultured and then changes in tight junction function of the endothelial cells were examined after addition of GDNF, in terms of transendothelial electrical resistance (TER) and permeability. GDNF at concentrations of 0.1 and 1 ng/ml significantly activated the barrier function of the endothelial cells in the presence of cAMP. Since GDNF is secreted from astrocytes sheathing capillary endothelial cells in the brain cortex, our results strongly suggest that GDNF enhances the barrier function of tight junctions of the BBB on the one hand, and also supports the survival of neurons on the other hand.

摘要

由于有一种观点认为，一种神经胶质细胞——星形胶质细胞，在血脑屏障（BBB）的分化过程中发挥着重要作用，因此我们研究了胶质细胞源性神经营养因子（GDNF）与血脑屏障之间的关系。首先，对大鼠大脑皮层进行免疫组织化学检查发现，胶质细胞源性神经营养因子受体（GFRalpha1）优先表达于毛细血管内皮细胞的细胞膜上。其次，为了阐明GDNF对血脑屏障的影响，我们培养了从猪大脑皮层分离出的毛细血管内皮细胞，然后在添加GDNF后，从跨内皮电阻（TER）和通透性方面检测内皮细胞紧密连接功能的变化。在存在环磷酸腺苷（cAMP）的情况下，浓度为0.1和1 ng/ml的GDNF显著激活了内皮细胞的屏障功能。由于GDNF是由包裹大脑皮层毛细血管内皮细胞的星形胶质细胞分泌的，我们的研究结果有力地表明，GDNF一方面增强了血脑屏障紧密连接的屏障功能，另一方面也支持神经元的存活。