神经免疫文献阅读第2期：Nature Neurosci—小胶质细胞研究重磅：TDP-43和脂滴调控小胶质细胞活性和无瘢痕再生

中文摘要

减少病理性小胶质细胞的激活对于预防慢性炎症和组织瘢痕形成至关重要。在这项研究中，研究人员使用斑马鱼的刺伤损伤模型，鉴定了一种损伤诱导的小胶质细胞状态，其特征是脂滴和43kDa的TAR DNA结合蛋白（TDP-43）的积聚。颗粒蛋白介导的脂滴和TDP-43+聚合物的清除是促进小胶质细胞恢复到基础状态并实现无瘢痕再生的必要条件和充分条件。此外，在创伤性脑损伤患者的死后皮质脑组织中，小胶质细胞的激活程度与脂滴和TDP-43+冷凝物的积累相关。总之，他们的结果揭示了损伤后小胶质细胞恢复到非激活状态所需的机制，这在人类中具有新的治疗应用潜力。

英文摘要

Decreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43)+ condensates. Granulin-mediated clearance of both lipid droplets and TDP-43+ condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration. Moreover, in postmortem cortical brain tissues from patients with traumatic brain injury, the extent of microglial activation correlated with the accumulation of lipid droplets and TDP-43+ condensates. Together, our results reveal a mechanism required for restoring microglia to a nonactivated state after injury, which has potential for new therapeutic applications in humans.

参考文献：TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury. Nat Neurosci. 2022 Nov 24. doi: 10.1038/s41593-022-01199-y. Online ahead of print.

微信视频预览查看