Acute liver damage generates age independent microglia morphology changes in mice.

Non-alcoholic fatty liver disease (NAFLD) has emerged as a silent global epidemic, frequently contributing to systemic inflammation. As the primary immune cells of the central nervous system (CNS), microglia undergo morphological changes that serve as critical indicators of CNS health. In this study, we aimed to quantify alterations in microglial morphology within the cortex of young and aged mice with liver damage. Our results demonstrated that hepatic dysfunction leads to a significant increase in total branch length in both young (285.79±68.23 μm) and aged animals (268.67±69.06 μm), compared to their respective controls (164.07±33.05 μm and 140.96±27.18 μm) (p<0.0001). Additionally, aged animals with liver damage exhibited a mean branch length of 5.84±0.66 μm, higher than 2.63±0.19 μm observed in those without liver injury. The number of primary branches in aged mice with liver damage decreased from 6.6±1.2 branches to 3.1±1.5 (p<0.0001). In addition, we have shown a decrease in the number of secondary branches in aged animals with liver damage. This suggests that microglia not only respond to CNS-specific injuries but also to chronic systemic pathologies like NAFLD. These findings highlight the importance of better understanding the liver-brain axis in order to better understand the neuroimmune consequences of systemic diseases.