Expression of MAPK and Inflammasomes in Brain Cells in Experimental Alzheimer’s Disease
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Introduction: Alzheimer’s disease is a chronic neurodegenerative disease leading to neuropsychiatric disorders and cognitive decline. A number of studies demonstrate an important role of the mitogen-activated protein kinase (MAPK) pathway and NLRP3 inflamasomes in β-amyloid metabolism impairment and insulin resistance in Alzheimer’s disease. Objective: To study the expression of NLRP3 in the cells of neuronal and glial nature, as well as the expression of MAPK in the amygdala neurons in animals with experimental Alzheimer’s disease. Materials and methods: Subjects of the study: (1) CD1 mice (males, 4 months old) divided in 2 groups, the experimental group (intra-hippocampal exposure to β-amyloid) and the control group (sham-operated animals); (2) mice with a genetic model of Alzheimer’s disease, the B6SLJ-line Tg (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas (males, 12 months old) and the corresponding control group, C57BL/6xSJL mice (males, 12 months old). Immunohistochemistry on free-floating sections was applied for the study of NLRP3 and MAPK expression in the brain amygdala. Results: We revealed the statistically significant increase in the number of NeuN/NLRP3-positive cells (p = 0.043) of the amygdala in animals with a genetic model of Alzheimer’s disease (29.05 ± 2.67) compared with the control group of animals (17.10 ± 1.95). A same trend was obvious in β-amyloid-induced neurodegeneration (p = 0.021). Intra-hippocampal exposure to β-amyloid caused the decrease of MAPK expression in the amygdala neurons (5.97 ± 0.66) compared with the sham-operated animals (13.25 ± 2.65) (p = 0.018). This was also seen in animals with a genetic model of the Alzheimer’s disease (p = 0.031). Conclusions: The increase of NLRP3 inflammasomes expression in animals with experimental Alzheimer’s disease was found in neurons, but not in astrocytes, along with a decrease of the MAPK expression in neurons of the amygdala. These findings indicate coupling of the inflammatory process and the disorganization on the insulin-signaling mechanisms of the brain during neurodegeneration.
Keywords:MAPK NLRP3 neuroinflammation insulin resistance Alzheimer’s disease
The study was funded by the grant of the President of the Russian Federation given to Russian Leading Research Teams (NSh10241.2016.7).
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