Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
Nat Commun. 2011 Feb 8;2:189. doi: 10.1038/ncomms1190.
Glia, the support cells of the central nervous system, have recently attracted considerable attention both as mediators of neural cell survival and as sources of neural regeneration. To further elucidate the role of glial and neural cells in neurodegeneration, we generated TrkB(GFAP) and TrkB(c-kit) knockout mice in which TrkB, a receptor for brain-derived neurotrophic factor (BDNF), is deleted in retinal glia or inner retinal neurons, respectively. Here, we show that the extent of glutamate-induced retinal degeneration was similar in these two mutant mice. Furthermore in TrkB(GFAP) knockout mice, BDNF did not prevent photoreceptor degeneration and failed to stimulate Müller glial cell proliferation and expression of neural markers in the degenerating retina. These results demonstrate that BDNF signalling in glia has important roles in neural protection and regeneration, particularly in conversion of Müller glia to photoreceptors. In addition, our genetic models provide a system in which glia- and neuron-specific gene functions can be tested in central nervous system tissues in vivo.
胶质细胞是中枢神经系统的支持细胞，最近作为神经细胞存活的介质以及神经再生的来源受到了相当大的关注。为了进一步阐明胶质细胞和神经细胞在神经退行性变中的作用，我们分别在视网膜胶质细胞和内视网膜神经元中缺失脑源性神经营养因子（BDNF）的受体 TrkB 的情况下，生成了 TrkB(GFAP) 和 TrkB(c-kit) 敲除小鼠。在这里，我们表明这两种突变小鼠中谷氨酸诱导的视网膜变性的程度相似。此外，在 TrkB(GFAP) 敲除小鼠中，BDNF 不能防止光感受器变性，也不能刺激 Müller 胶质细胞在变性视网膜中的增殖和神经标记物的表达。这些结果表明，BDNF 在胶质细胞中的信号转导在神经保护和再生中具有重要作用，特别是在 Müller 胶质细胞向光感受器的转化中。此外，我们的遗传模型为中枢神经系统组织中胶质细胞和神经元特异性基因功能的体内测试提供了一个系统。
