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Updated: May 20, 2025

In Vivo Chronic Two-Photon Imaging of Microglia in the Mouse Hippocampus
Published on: July 6, 2022
Morphological Differences in Hippocampal Microglia in C57BL/6N Mice with Liver Injury and Depressive-Like Behavior
Gabriel Nedelea1, Mădălina Iuliana Mușat1, Smaranda Ioana Mitran1,2
1Experimental Research Centre for Normal and Pathological Aging, University of Medicine and Pharmacy of Craiova, Petru Rares Street 2, 200349, Craiova, Dolj, Romania.
Introduction:
Microglia, one of the most important cells of the central nervous system, undergo specific changes depending on the pathology. It has been reported that both depressive disorders and liver diseases generate hippocampal changes and neuroinflammation. However, the combined effects of the two pathologies on microglia morphology in the hippocampus have not been sufficiently explored.
Material And Methods:
In this study, we analyzed the morphological changes of the hippocampal microglia using confocal microscopy and a semi-manual method of quantification. We focused on total branch length, the branch number and the mean branch length. C57BL/6N mice were used and subjected to a methionine and choline deficient diet (MCD) to induce liver damage, and a chronic unpredictable mild stress (CUMS) procedure for depressive-like behavior.
Results:
We were able to show that CUMS protocol and MCD diet led to a reduction in total branch length, branch number and mean branch length. Also, CUMS alone was associated with a decrease in the number of secondary and terminal branches.
Conclusion:
Our study showed that depressive-like behavior and liver damage influence microglial morphology in the hippocampus, and it may be considered in future research of these intricate pathologies.
Insights
Depressive-like behavior and liver damage significantly alter hippocampal microglia morphology in mice. Both conditions reduced microglial branching, indicating neuroinflammation relevant to these complex conditions.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia, the central nervous system's immune cells, exhibit morphological changes in response to various pathologies.
- Both depressive disorders and liver diseases are known to induce hippocampal changes and neuroinflammation.
- The combined impact of depression and liver disease on hippocampal microglia morphology remains under-explored.
Purpose of the Study:
- To investigate the morphological alterations of hippocampal microglia under combined depressive-like behavior and liver damage.
- To quantify changes in microglial branching metrics, including total branch length, branch number, and mean branch length.
Main Methods:
- Utilized C57BL/6N mice subjected to a methionine and choline deficient (MCD) diet to induce liver damage.
- Employed a chronic unpredictable mild stress (CUMS) procedure to model depressive-like behavior.
- Analyzed hippocampal microglia morphology using confocal microscopy and semi-manual quantification of branching parameters.
Main Results:
- Both CUMS and MCD diet significantly reduced total branch length, branch number, and mean branch length of hippocampal microglia.
- CUMS alone was associated with a decrease in secondary and terminal branch numbers.
- These findings indicate a significant impact of combined pathologies on microglial structure.
Conclusions:
- Depressive-like behavior and liver damage demonstrably influence microglial morphology within the hippocampus.
- The observed morphological changes suggest a role for neuroinflammation in the interplay between these conditions.
- These findings warrant consideration in future research on the complex mechanisms underlying depression and liver disease.

