Expression of MAPK and inflammasomes in cells of the brain in experimental Alzheimer''s disease
Introduction. Alzheimer's disease is a chronic neurodegenerative disease that leads to neuropsychiatric disorders and decrease in cognitive activity. A number of studies demonstrate the important role of the mitogenactivated protein kinase (MAPK) pathway and inflamasome NLRP3 in disturbing the metabolism of βamyloid and insulin resistance in Alzheimer's disease. Objective. To study the expression of NLRP3 on cells of neuronal and glial nature, as well as MAPK on neurons in the amygdala of animals with experimental Alzheimer's disease. Material and methods. Subjects of the study were: 1) CD1 mice (males, 4 months old) divided in 2 groups, the experimental group (intrahippocampal intjection of βamyloid) and the control group (shamoperated animals); mice with a genetic model of Alzheimer’s disease, the B6SLJline Tg (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas (males, 12 months old) and the corresponding control group, C57BL/6xSJL mice (males, 12 months old). Immunohistochemistry on freefloating sections was used to study the expression of NLRP3 and MAPK in the brain amygdala. Results. It was found that NeuN/NLRP3positive cells were increased in animals with a genetic model of Alzheimer's disease in the amygdala (29.05±2.67) compared with the control animals (17.10±1.95) (p=0.043). A similar picture was observed in βamyloidinduced neurodegeneration (p=0.021). Intrahippocampal injection of βamyloid caused the decrease of MAPK expression in the amygdala neurons (5.97±0.66) compared with shamoperated animals (13.25±2.65) (p=0.018). A similar situation was observed in animals with a genetic model of Alzheimer's disease (p=0.031). Conclusion. Increase of expression of inflammasomes NLRP3 was observed on neurons, but not astrocytes, in animals with experimental Alzheimer's disease. We found a decrease of the expression of MAPK on neurons in the amygdala. This indicates coupling of the inflammatory process and the disturbances of insulinsignaling mechanisms in the brain in neurodegeneration.