PDF(Pubmed)
Abstract：
Stroke, trauma, and neurodegenerative disorders cause loss of neurites (axons and dendrites) in addition to neuronal death. Neurite loss may result directly from a primary insult, secondary to parental neuron death, or secondary to a post-injury inflammatory response. Here, we use lipopolysaccharide and the alarmin S100β to selectively evaluate neurite loss caused by the inflammatory response. Activation of microglia and infiltrating macrophages by these stimuli causes neurite loss that far exceeds neuronal death, both in vitro and in vivo. Neurite loss is accompanied by the formation of cofilactin rods and aggregates (CARs), which are polymers of cofilin-1 and actin induced by oxidative stress and other factors. Mice deficient in either cofilin-1 or the superoxide-generating enzyme NADPH oxidase-2 show reduced CAR formation, neurite loss, and motor impairment. The findings identify a mechanism by which inflammation leads to neurite loss via CAR formation and highlight the relevance of neurite loss to functional impairment.
摘要：
Stroke,创伤,神经退行性疾病除了神经元死亡外，还会导致神经突（轴突和树突）丢失。轴突丢失可能是由原发性侮辱直接造成的，继发于亲代神经元死亡，或继发于损伤后的炎症反应。这里,我们使用脂多糖和AlarminS100β来选择性地评估由炎症反应引起的神经突丢失。通过这些刺激激活小胶质细胞和浸润巨噬细胞会导致神经突损失，远远超过神经元死亡，在体外和体内。神经元丢失伴随着cofilactin杆和聚集体（CAR）的形成，它们是由氧化应激和其他因素诱导的cofilin-1和肌动蛋白的聚合物。缺乏cofilin-1或超氧化物生成酶NADPH氧化酶-2的小鼠显示出减少的CAR形成，神经突丢失，和运动障碍。该发现确定了炎症通过CAR形成导致神经突损失的机制，并强调了神经突损失与功能损害的相关性。
