Depressive-Like Behavior and Liver Damage Generate Behavioral and Cortical Microglial Morphological Differences in Mice.

Abstract

Introduction: The correlation between nonalcoholic fatty liver disease (NAFLD) and depression has already been established, but the relation between the two is insufficiently studied. Various murine models have proven effective in evaluating the mechanisms involved in these pathologies.

Material and methods: In this study we aimed to assess how the chronic unpredictable mild stress (CUMS) protocol impacts the behavior of mice with liver damage induced by a methionine choline deficient (MCD) diet, and also to evaluate the changes in microglial morphology in the cortex of animals with depressive-like behavior and liver injury. Thus, the cortical region was analyzed using confocal microscopy.

Results: Sucrose preference test and open field test revealed induced anhedonia and anxiety-like behavior, but short-term memory was not impaired, as assessed by novel object recognition test. Administration of the MCD diet led to an increase in total branch length and the number of terminal branches, revealing a hyperactivated microglia. The CUMS protocol in combination with MCD diet induced a reduced branching complexity, with fewer tertiary and terminal branches.

Conclusion: Our study highlights the importance of microglial morphology at the cortical level in coexisting depression and liver injury.