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

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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.

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About the authors

Alexandr D. Okhalnikov

Research Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences

Author for correspondence.
Email: a11o20@mail.ru
ORCID iD: 0000-0003-3244-6034
SPIN-code: 1895-6675
Russian Federation, Nizhny Novgorod; Tomsk

Maria S. Gavrish

Research Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod

Email: mary_gavrish@mail.ru
ORCID iD: 0000-0002-7867-8837
SPIN-code: 8116-0326
Russian Federation, Nizhny Novgorod

Alexey A. Babaev

Research Institute of Neurosciences, National Research Lobachevsky State University of Nizhny Novgorod

Email: alexisbabaev@list.ru
ORCID iD: 0000-0002-8150-6649
SPIN-code: 5705-7846

Cand. Sci. (Biol.), Associate Professor

Russian Federation, Nizhny Novgorod

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Supplementary files

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2. Fig. 1. 3D visualization of morphological subtypes of microglial cells in the sagittal sections of the cerebral cortex in groups “WT” (a) and “FAD” (b), the arrows indicate individual subtypes of cells. Representative enlarged 3D images of individual subtypes of microglia: resident (N 1A — c), dystrophic (N 3B — d) and amoeboid (N 2B — e). Red channel — Alexa Fluor 647 (EX/EM 652/668), coloring β-amyloid plaques; orange channel — Alexa Fluor 555 (EX/EM 555/565), coloring of the microglia marker — IBA1. Large-scale line — 10 μm.

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3. Fig. 2. Heterogenicity of microglia in the sagittal sections of the cortex of the brain of the 5xfad line mice. Red channel — Alexa Fluor 647 (EX/EM 652/668), coloring β-amyloid plaques; orange channel — Alexa Fluor 555 (EX/EM 555/565), coloring of the microglia marker — IBA1; arrows point to amyloid plaques; ×40.

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4. Fig. 3. Results of projection processing Z-steaks using the Skeleton plugin in the Imagej app. Red channel — Alexa Fluor 647 (EX/EM 652/668), coloring β-amyloid plaques; orange channel — Alexa Fluor 555 (EX/EM 555/565), coloring of the microglia marker — IBA1; ×40.

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5. Fig. 4. Assessment of density and medium branching of microclial cells in the sagittal sections of the cerebral cortex of the 5xFAD line mice: a — comparison of the average length of the processes of the solitary microclial cell; b — comparison of the density of microglial cells in a field of 22.56×10–8 m; с — distribution of world cells in medium branching; * statistically significant differences (р ≤0.05; Student’s t-test).

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6. Fig. 5. The results of fractal analysis of microglial cells in the sagittal sections of the cerebral cortex of the 5xfad line mice: a — the maximum distance between processes; b — the average distance from the catfish to the end of the processes; c — fractal dimension; d — paintings; * statistically significant differences (p ≤0.05; Student’s t-test).

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