Department of Anesthesiology, Affiliated Hospital of Nantong University, #20 Xisi Road, Nantong 226001, Jiangsu, China.
Department of Pharmacology, School of Pharmacy, Nantong University, #19 Qixiu Road, Nantong 226001, Jiangsu, China; Department of Neuroscience & Cell Biology, Rutgers-Robert Wood Johnson Medical School, 675 Hoes lane, Piscataway, 08854, NJ, United States.
Pharmacol Res. 2019 Jan;139:286-297. doi: 10.1016/j.phrs.2018.11.028. Epub 2018 Nov 23.
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 elongation in vitro and in vivo, aiming to further drive the understanding of microglial process plasticity.
小胶质细胞是大脑中一种具有分支形态的神经胶质细胞，对于清除神经元碎片和限制病变部位的扩展至关重要。在适度激活时，它们的形态发生转变，从而产生有益的反应。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治疗神经炎症相关疾病的有效策略。在这种病理性激活过程中，小胶质细胞的突起长度也会缩短，这有助于这些疾病的发病机制。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，另一个是它们突起的动态变化。前者在以前的研究中已有很好的记载，而后者在很大程度上仍然未知。最近，我们和其他人报道了小胶质细胞突起的伸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会使小胶质细胞失去限制病理性损伤的能力，而小胶质细胞突起的伸长有助于减轻神经炎症。与传统的抗炎策略相比，刺激小胶质细胞突起的伸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，从而使其体内平衡调节更加有效。在这篇综述中，我们讨论了体外和体内调节小胶质细胞突起伸长的因素，旨在进一步推动对小胶质细胞突起可塑性的理解。
