Microglia Are Irrelevant for Neuronal Degeneration and Axon Regeneration after Acute Injury
Microglia Are Irrelevant for Neuronal Degeneration and Axon Regeneration after Acute Injury
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DOI：
10.1523/jneurosci.0584-17.2017
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发表时间：
2017-06-21
影响因子：
5.3
通讯作者：
Fischer, Dietmar
中科院分区：
文献类型：
--
作者：
Hilla, Alexander M.;Diekmann, Heike;Fischer, Dietmar
小胶质细胞在神经系统损伤后的退行性和再生过程中的作用仍然不明确，部分原因是缺乏适当的研究方法。在这里，我们表明，治疗与药理集落刺激因子1受体抑制剂PLX5622特异性消除小胶质细胞在小鼠视网膜和视神经的高效率。有趣的是，视神经挤压后视网膜神经节细胞（RGC）变性的时间过程和程度不受小胶质细胞耗竭的影响，尽管这些动物的视网膜中未清除预标记的凋亡RGC的残留物。此外，小胶质细胞耗竭既不影响视神经损伤后再生相关基因的诱导，也不影响透镜损伤（LI）后RGCs再生潜力的增加。然而，尽管小胶质细胞耗竭后星形胶质细胞对视神经损伤部位的再增殖显著延迟，但PLX5622治疗或氯膦酸盐脂质体治疗对外周巨噬细胞耗竭不影响自发和LI诱导的轴突再生。只有同时双耗尽小胶质细胞和浸润的巨噬细胞轻微，但显着，损害视神经再生。因此，小胶质细胞在急性CNS损伤后基本上不参与RGC变性或轴突再生。
The role of microglia in degenerative and regenerative processes after damage of the nervous system remains ambiguous, partially due to the paucity of appropriate investigative methods. Here, we show that treatment with the pharmacological colony stimulating factor 1 receptor inhibitor PLX5622 specifically eliminated microglia in murine retinae and optic nerves with high efficiency. Interestingly, time course and extent of retinal ganglion cell (RGC) degeneration after optic nerve crush remained unaffected upon microglia depletion, although remnants of prelabeled apoptotic RGCs were not cleared from the retina in these animals. In addition, microglia depletion neither affected the induction of regeneration associated genes upon optic nerve injury nor the increased regenerative potential of RGCs upon lens injury (LI). However, although the repopulation of the optic nerve lesion site by astrocytes was significantly delayed upon microglia depletion, spontaneous and LI-induced axon regeneration were unaffected by PLX5622 treatment or peripheral macrophage depletion by clodronate liposome treatment. Only concurrent double depletion of microglia and infiltrated macrophages slightly, but significantly, compromised optic nerve regeneration. Therefore, microglia are not essentially involved in RGC degeneration or axonal regeneration after acute CNS injury.