Regulation of microglial process elongation, a featured characteristic of microglial plasticity

The elongation of microglial process is tightly associated with the transformation of microglia from a pro-inflammatory to an anti-inflammatory status. In this review, we summarize the factors that regulate microglial process plasticity. Some endogenous substances, such as SB, BHB, ATP, and adenosine, can promote microglial process elongation. Ion channels or transporters, such as the Cl− channel, the THIK-1 channel, and the K+-Cl− co-transporter, are involved in microglial process regulation. Other factors that regulate microglial process plasticity include luteolin, MACRO, compound C, Runx1, IL-4, IL-13, IL-10, Vitamin E, Vitamin C, GM1, TG, and CaM. [Display omitted] 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 proc