Morphological features of microglial cells in a 5xFAD mouse model of Alzheimer's disease

Abstract

BACKGROUND: Aging is an inevitable and irreversible process associated with increased risk of developing various neurodegenerative diseases, one of which is Alzheimer's disease. Currently, the role of glial cells, in particular microglia, in the pathogenesis of Alzheimer's disease is being actively studied. However, only a few studies have correlated the morphological features of microglia and their spatial arrangement in relation to β-amyloid plaques.

AIM: Describe the main morphological parameters of microglia in the 5xFAD mouse model of Alzheimer's disease at a late stage of pathology development.

METHODS: As the studied object, mice were chosen by the age of 15–16 months of the 5xFAD line, as a model of acceleid amyloidosis. The immunohistochemical staining of the study of the morphological diversity of microglia was carried out on the cuts of the cortex of the mouse brain. The obtained confocal images performed an immunogystological analysis of the cuts of the cerebral cortex when analyzed using the Imagej application using the plugins of Skeleton, AnalyzeSkeleton (2D/3D) and FracLac.

RESULTS: During the study, 5xFAD mice were divided into two groups (n=3 each). Carriers of the app and psen1 transgenes were assigned to the “FAD” group, and wild-type mice were assigned to the “Wt” group (control). We analyzed 3–4 sagittal sections (50 µm) of the brain from each mouse. The results showed that microglial cells from mice with signs of Alzheimer's disease have smaller fractal dimension, lacunarity and branching.

CONCLUSION: The presence of β-amyloid plaques contributes to the migration of microglia to the focus of inflammation, its proliferation and transition to the phagocytic and dystrophic subtype. According to fractal analysis, there is a significant (p ≤0.05) decrease in the average branching of microglial processes, a decrease in fractal dimension and lacunarity.

Keywords

Alzheimer's disease / microglia / cell morphology / immunohistochemistry / 5xFAD

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