KRIBB11: A Promising Drug that Promotes Microglial Process Elongation and Suppresses Neuroinflammation.

Microglia are key components of the central innate immune system. The over-activation of microglia, which occurs in nervous system disorders, is usually accompanied with retractions of their ramified processes. Reversing of microglial process retraction is a potential strategy for the prevention of neuroinflammation. Our previous studies have reported some endogenous molecules and drugs that can promote microglial process elongation at conditions in vitro and in vivo , such as butyrate and β-hydroxybutyrate, sulforaphane, and diallyl disulfide. Here, reported another compound that can promote microglial process elongation. We found that KRIBB11, a compound which has been reported to suppress nitric oxide production in microglia, induced significant elongations of the processes in microglia in cultured and in vivo conditions in a reversible manner. KRIBB11 pretreatment also prevented lipopolysaccharide (LPS)-induced shortenings of microglial process in cultured conditions and in vivo conditions, inflammatory responses in primary cultured microglia and the prefrontal cortex, and depression-like behaviors in mice. Mechanistic studies revealed that KRIBB11 incubation up-regulated phospho-Akt in cultured microglia and Akt inhibition blocked the pro-elongation effect of KRIBB11 on microglial process in cultured conditions and in vivo conditions, suggesting that the regulatory effect of KRIBB11 is Akt-dependent. Akt inhibition was also found to abrogate the preventive effect of KRIBB11 on LPS-induced inflammatory responses in primary cultured microglia and prefrontal cortexes as well as LPS-induced depression-like behaviors in mice. Collectively, our findings demonstrated that KRIBB11 is a novel compound that can prevent microglial activation and neuroinflammation-associated behavioral deficits possibly through inducing the Akt-mediated elongation of microglial process.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Su, Dou, Hong, Xu, Lu, Lu, Ye and Huang.)