Impaired neurite outgrowth in the retina of a murine model of Sandhoff disease
Impaired neurite outgrowth in the retina of a murine model of Sandhoff disease
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DOI：
10.1167/iovs.05-0038
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发表时间：
2005-09-01
影响因子：
4.4
通讯作者：
Yamanaka, S
中科院分区：
文献类型：
--
作者：
Sango, K;Takano, M;Yamanaka, S
目的.目的：研究溶酶体沉积对G（M2）神经节苷脂沉积症（Sandhoff病）小鼠模型视网膜形态学和突起生长能力的影响。用光镜和电镜观察了3月龄和4月龄Sandhoff（SD）小鼠视网膜的组织学表现。将1、2和4月龄的SD小鼠和野生型（WT）小鼠的视网膜在存在或不存在脑源性神经营养因子（BDNF）的胶原凝胶中培养，并检查神经突生长。形态学研究显示，G（M2）神经节苷脂在SD小鼠视网膜神经节细胞中以时间依赖性方式积累。培养7天和10天后，2月龄和4月龄SD小鼠视网膜外植体的神经突数量显著低于年龄匹配的WT小鼠。BDNF的应用显着改善了2月龄时SD和WT小鼠视网膜的神经突生长。在4月龄时，BDNF在刺激SD小鼠视网膜神经突生长方面的效果远低于WT小鼠。这些结果表明，G（M2）神经节苷脂的溶酶体储存损害了培养的视网膜神经节细胞中神经突生长的能力，BDNF在疾病的早期阶段有效地减少了这种损害。
PURPOSE. To investigate the effects of lysosomal storage on the morphologic appearance and the neurite outgrowth capability of the retina in a mouse model of G(M2) gangliosidosis ( Sandhoff disease).METHODS. Histopathologic appearances of retinas in Sandhoff (SD) mice at 3 and 4 months of age were examined by light and electron microscopy. Retinas of SD mice and wild-type (WT) mice at 1, 2, and 4 months of age were cultured in collagen gel in the presence or absence of brain-derived neurotrophic factor ( BDNF), and neurite outgrowth was examined.RESULTS. Morphologic studies revealed accumulation of G(M2) ganglioside in the retinal ganglion cells of SD mice in a time-dependent manner. The number of neurites from the retinal explants after 7 and 10 days in culture were significantly lower in 2- and 4-month-old SD mice than in the age-matched WT mice. The application of BDNF significantly improved neurite outgrowth from the retina in both SD and WT mice at 2 months of age. At 4 months of age, BDNF was much less effective at stimulating neurite outgrowth in the retina of SD mice than in retina of WT mice.CONCLUSIONS. These results indicate that lysosomal storage of G(M2) ganglioside impairs the capability of neurite outgrowth in retinal ganglion cells in culture and that BDNF is effective at diminishing this impairment during the early stage of the disease.