Exosomes from Inflamed Macrophages Promote the Progression of Parkinson’s Disease by Inducing Neuroinflammation
Exosomes from Inflamed Macrophages Promote the Progression of Parkinson’s Disease by Inducing Neuroinflammation
复制标题
DOI：
10.1007/s12035-022-03179-6
复制
发表时间：
2023-01
影响因子：
5.1
通讯作者：
Yan Jin;Runze Wu;Li Li-Li;Li-hua Shen;Yunjuan Gu;Cheng Sun
中科院分区：
文献类型：
--
作者：
Yan Jin;Runze Wu;Li Li-Li;Li-hua Shen;Yunjuan Gu;Cheng Sun
炎症是帕金森氏病(PD)和肥胖相关代谢综合征的共同特征。白色脂肪组织中炎症的巨噬细胞介导的炎症在代谢综合征的发病机制中起着关键作用。外切体是连接周围组织和中枢神经系统的重要载体。因此，我们推测炎性巨噬细胞来源的外切体可能参与了帕金森病的病理过程。在这里，我们从脂多糖或干扰素γ处理的巨噬细胞(炎症巨噬细胞)中制备外切体，并研究它们在帕金森病中的潜在作用。我们的数据显示，发炎巨噬细胞的外切体能刺激原代小胶质细胞和星形胶质细胞中促炎细胞因子的表达。在体内，发炎的巨噬细胞外切体导致小鼠的行为缺陷，表现为旋转试验中持续时间的缩短和杆状试验中潜伏期的延长。外切体的处理也减少了黑质致密部(SNPC)和纹状体的酪氨酸羟化酶(TH)阳性细胞。所有这些PD样表型可能是由于炎症巨噬细胞的外切体诱导小胶质细胞和星形胶质细胞激活所致。外切体测序，结合生物信息学分析和功能研究，揭示了外切体miRNAs，如miR-155-5p，可能是诱导神经胶质细胞炎症反应的关键因素。这些结果表明，发炎的巨噬细胞来源的外切体可能是帕金森病发生的原因之一。在这一点上，炎症的巨噬细胞外体可能是一个连接物，将周围组织的炎症传递到中枢神经系统。
Inflammation is a common feature both for Parkinson’s disease (PD) and obesity-associated metabolic syndromes. Inflammation mediated by inflamed macrophages in white adipose tissue plays a pivotal role for the pathogenesis of metabolic syndromes. Exosomes are important carriers connecting peripheral tissues and the central nervous system (CNS). Therefore, we speculate that exosomes derived from inflamed macrophages may be involved in the pathological progression of PD. Here, we prepared exosomes from lipopolysaccharide (LPS) or interferon gamma (IFNγ) treated macrophages (inflamed macrophages) and examined their potential roles in PD. Our data showed that exosomes from inflamed macrophages stimulate proinflammatory cytokine expression in primary microglia and astrocytes. In vivo, inflamed macrophage exosomes induce behavioral defects in mice as evidenced by shortened duration in the rotarod test and prolonged latency in the pole test. The treatment of exosomes also reduces tyrosine hydroxylase (TH) positive cells in the substantia nigra pars compacta (SNpc) and striatum. All these PD-like phenotypes are likely due to the activation of microglia and astrocytes induced by exosomes from inflamed macrophages. Exosome sequencing, together with bioinformatics analysis and functional studies, revealed that exosomal miRNAs such as miR-155-5p are likely a key factor for inducing an inflammatory response in glial cells. These results indicate that exosomes derived from inflamed macrophages are likely a causative factor for developing PD. In this regard, inflamed macrophage exosomes might be a linker transducing the peripheral tissue inflammation into the CNS.