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. 2024 Oct-Dec;50(5):577-584.
doi: 10.12865/CHSJ.50.04.12. Epub 2024 Dec 31.

Morphological Differences in Hippocampal Microglia in C57BL/6N Mice with Liver Injury and Depressive-Like Behavior

Affiliations

Morphological Differences in Hippocampal Microglia in C57BL/6N Mice with Liver Injury and Depressive-Like Behavior

Gabriel Nedelea et al. Curr Health Sci J. 2024 Oct-Dec.

Abstract

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.

Keywords: Morphology; NAFLD; depression; hippocampus; microglia.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Schematic overview of the methodology used. (A) Imaging of microglial cells in the mouse hippocampus. (B) A representative microglial cell (within the white square), illustrating the soma and fine processes. Each analyzed cell was (C) isolated, (D) manually traced, and (E) subsequent verified. Scale bar: 20μm.
Figure 2
Figure 2
Microglial arbor morphology in hippocampus: The detailed morphology of microglia was assessed through a systematic analysis of individual branches, focusing on key parameters, including (A) total arbor length, (B) branch count, and (C) mean branch length. Representative images of microglia from each experimental group: (D) WT, (E) MCD, (F) CUMS, and (G) CUMS+MCD. Data are shown as mean±SD, with statistical significance represented as *p<0.05, ***p<0.001, and ****p<0.0001.
Figure 3
Figure 3
Detailed morphological analysis comparing differences between the number of (A) primary, (B) secondary, (C) tertiary, (D) quaternary and (E) terminal branches. Data are shown as mean±SD, with statistical significance represented as *p<0.05.

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