A role for caveolin-1 in post-injury reactive neuronal plasticity
A role for caveolin-1 in post-injury reactive neuronal plasticity
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DOI：
10.1111/j.1471-4159.2004.02917.x
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发表时间：
2005-02-01
影响因子：
4.7
通讯作者：
Poirier, J
中科院分区：
文献类型：
--
作者：
Gaudreault, SB;Blain, JF;Poirier, J
成人大脑的重塑和可塑性需要胆固醇的重新分布和合成，以形成新的膜成分。Caveolin-1是一种与胆固醇结合的膜蛋白，参与细胞内胆固醇的转运和稳态。这里提出的证据表明，在海马中的小窝蛋白-1的上调，这是暂时相关的突触素增加在神经再支配阶段在海马去传入的小鼠模型。使用神经元反应可塑性的体外模型，我们研究了病毒介导的小窝蛋白-1过表达对经历终末重塑的受损分化PC 12细胞的影响。损伤后三天，小窝蛋白-1过表达的细胞显示突触素和GAP-43增加，这两个标记物是神经突发芽和突触发生。在形态学上，小窝蛋白-1过表达的细胞表现出初级神经突生长和分支的减少以及神经突密度的增加。小窝蛋白-1-过表达的细胞也揭示了存在的终端肿胀和串珠沿着过程，与微管稳定性的可能改变一致。此外，小窝蛋白-1的免疫荧光的焦点富集在小鼠原代海马神经元的轴突和树突终末的基础上观察。总之，这些结果表明，小窝蛋白-1在成年中枢神经系统损伤诱导的突触和终末重塑的调节中起着积极的作用。
Remodeling and plasticity in the adult brain require cholesterol redistribution and synthesis for the formation of new membrane components. Caveolin-1 is a cholesterol-binding membrane protein involved in cellular cholesterol transport and homeostasis. Evidence presented here demonstrates an up-regulation of caveolin-1 in the hippocampus, which was temporally correlated with an increase in synaptophysin during the reinnervation phase in a mouse model of hippocampal deafferentation. Using an in vitro model of neuronal reactive plasticity, we examined the effect of virally mediated overexpression of caveolin-1 on injured differentiated PC12 cells undergoing terminal remodeling. Three days post lesion, caveolin-1-overexpressing cells revealed increases in synaptophysin and GAP-43, two markers of neurite sprouting and synaptogenesis. Morphologically, caveolin-1-overexpressing cells showed a decrease in primary neurite outgrowth and branching as well as an increase in neurite density. Caveolin-1-overexpressing cells also revealed the presence of terminal swelling and beading along processes, consistent with a possible alteration of microtubules stability. Moreover, a focal enrichment of caveolin-1 immunofluorescence was observed at the bases of axonal and dendritic terminals of mouse primary hippocampal neurons. Altogether, these results indicate that caveolin-1 plays an active role in the regulation of injury-induced synaptic and terminal remodeling in the adult CNS.