Regulation of microglial process elongation, a featured characteristic of microglial plasticity
Regulation of microglial process elongation, a featured characteristic of microglial plasticity
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DOI：
10.1016/j.phrs.2018.11.028
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发表时间：
2019-01
影响因子：
9.3
通讯作者：
Rongrong Yang;Hui Wang;J. Wen;Kai-Li Ma;Dongjian Chen;Zhuo Chen;Chao Huang
中科院分区：
文献类型：
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作者：
Rongrong Yang;Hui Wang;J. Wen;Kai-Li Ma;Dongjian Chen;Zhuo Chen;Chao Huang
小神经胶质细胞是脑内的一种神经胶质细胞，其特征在于分枝形态，对于去除神经元碎片和限制病变部位的扩张至关重要。在中度激活后，它们经历形态学的转变，诱导有益的反应。然而，在强烈刺激下，它们通过产生促炎细胞因子介导神经元损伤。抑制这种级联反应被认为是神经炎症相关疾病治疗的有效策略。在这种病理激活过程中，小胶质细胞也经历了过程长度的缩短，这有助于这种疾病的发病机制。因此，小胶质细胞的可塑性应该被认为有两个组成部分：一个是炎症介质的产生，另一个是它们过程中的动态变化。前者的作用在以前的研究中已经有了很好的记录，而后者在很大程度上仍然是未知的。最近，我们和其他人报道了小胶质细胞突起的延长与小胶质细胞从促炎状态向抗炎状态的转变有关，这表明突起长度的缩短将使小胶质细胞失去限制病理损伤的能力，而小胶质细胞突起的延长将有助于减轻神经炎症。与传统的抗神经炎症策略相比，刺激小胶质细胞突起的延长不仅减少了促炎细胞因子的产生，而且恢复了小胶质细胞扫描其周围环境的能力，从而使其稳态调节更有效。本文就小胶质细胞突起在体内和体外的延伸调节因素进行综述，旨在进一步加深对小胶质细胞突起可塑性的认识。
Microglia, a type of glia within the brain characterized by a ramified morphology, are essential for removing neuronal debris and restricting the expansion of a lesion site. Upon moderate activation, they undergo a transformation in morphology inducing beneficial responses. However, upon strong stimulation, they mediate neuronal damage via production of pro-inflammatory cytokines. The inhibition of this cascade is considered an effective strategy for neuroinflammation-associated disorder therapy. During this pathological activation microglia also undergo a shortening of process length which contributes to the pathogenesis of such disorders. Thus, microglial plasticity should be considered to have two components: one is the production of inflammatory mediators, and the other is the dynamic changes in their processes. The former role has been well-documented in previous studies, while the latter one remains largely unknown. Recently, we and others have reported that the elongation of microglial process is associated with the transformation of microglia from a pro-inflammatory to an anti-inflammatory state, suggesting that the shortening of process length would make the microglia lose their ability to restrict pathological injury, while the elongation of microglial process would help attenuate neuroinflammation. Compared with the traditional anti-neuroinflammatory strategy, stimulating elongation of microglial process not only reduces the production of pro-inflammatory cytokines, but restores the ability of microglia to scan their surrounding environments, thus rendering their homeostasis regulation more effective. In this review, we provide a discussion of the factors that regulate microglial process elongationin vitroandin vivo, aiming to further drive the understanding of microglial process plasticity.