Abstract
Aims:
This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation.
Methods:
Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment.
Results:
Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation.
Conclusion:
Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia.
Keywords:
TCA cycle; acetylation; citrate synthase; microglia; neuroinflammation; traumatic brain injury.