ApoD, a Glia-Derived Apolipoprotein, Is Required for Peripheral Nerve Functional Integrity and a Timely Response to Injury
ApoD, a Glia-Derived Apolipoprotein, Is Required for Peripheral Nerve Functional Integrity and a Timely Response to Injury
复制标题
DOI：
10.1002/glia.21010
复制
发表时间：
2010-08-15
期刊：
影响因子：
6.2
通讯作者：
Sanchez, Diego
中科院分区：
文献类型：
--
作者：
Ganfornina, Maria D.;Do Carmo, Sonia;Sanchez, Diego
神经胶质细胞是轴突再生过程中的关键因素，可促进或抑制轴突生长。损伤诱导的神经胶质衍生因子的研究对于理解允许或阻止再生的过程非常重要，并且可以解释为什么PNS具有显著的再生能力，而CNS则没有。在这项工作中，我们重点研究载脂蛋白D (ApoD)，一种由PNS和CNS神经胶质细胞表达的脂质体蛋白。ApoD的表达在PNS损伤时被强烈诱导，但其作用尚未阐明。在这里，我们发现ApoD是必需的：(1)随着年龄的增长维持周围神经功能和组织稳态，(2)对损伤做出充分和及时的反应。我们使用ApoD敲除和过表达人ApoD的转基因小鼠研究两岁时的坐骨神经损伤。ApoD的缺乏使完整神经的运动神经传导速度和髓鞘厚度降低。在损伤后，我们分析了一组损伤诱导基因的功能恢复、细胞过程以及蛋白质和mRNA表达谱。ApoD有助于恢复损伤后的运动功能，促进髓磷脂清除，调节血管生成的程度和巨噬细胞募集到损伤部位的数量。轴突再生和髓鞘再生在没有ApoD的情况下被延迟，并被过量的ApoD刺激。mRNA和蛋白表达谱显示，ApoD在功能上以年龄依赖的方式与损伤触发的特定分子程序相关。(C) 2010 Wiley-Liss, Inc。
Glial cells are a key element to the process of axonal regeneration, either promoting or inhibiting axonal growth. The study of glial derived factors induced by injury is important to understand the processes that allow or preclude regeneration, and can explain why the PNS has a remarkable ability to regenerate, while the CNS does not. In this work we focus on Apolipoprotein D (ApoD), a Lipocalin expressed by glial cells in the PNS and CNS. ApoD expression is strongly induced upon PNS injury, but its role has not been elucidated. Here we show that ApoD is required for: (1) the maintenance of peripheral nerve function and tissue homeostasis with age, and (2) an adequate and timely response to injury. We study crushed sciatic nerves at two ages using ApoD knock-out and transgenic mice over-expressing human ApoD. The lack of ApoD decreases motor nerve conduction velocity and the thickness of myelin sheath in intact nerves. Following injury, we analyze the functional recovery, the cellular processes, and the protein and mRNA expression profiles of a group of injury-induced genes. ApoD helps to recover locomotor function after injury, promoting myelin clearance, and regulating the extent of angiogenesis and the number of macrophages recruited to the injury site. Axon regeneration and remyelination are delayed without ApoD and stimulated by excess ApoD. The mRNA and protein expression profiles reveal that ApoD is functionally connected in an age-dependent manner to specific molecular programs triggered by injury. (C) 2010 Wiley-Liss, Inc.