Анналы клинической и экспериментальной неврологии (Dec 2017)

Expression of MAPK and inflammasomes in cells of the brain in experimental Alzheimer's disease

  • Yana V. Gorina,
  • Olga L. Lopatina,
  • Yuliya K. Komleva,
  • Anatolii I. Chernykh,
  • Alla B. Salmina

DOI
https://doi.org/10.18454/ACEN.2017.4.5
Journal volume & issue
Vol. 11, no. 4
pp. 45 – 51

Abstract

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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 mitogen-activated protein kinase (MAPK) pathway and inflamasome NLRP3 in disturbing the metabolism of -amyloid 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 (intra-hippocampal intjection of -amyloid) and the control group (sham-operated animals); mice with a genetic model of Alzheimers 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 used to study the expression of NLRP3 and MAPK in the brain amygdala. Results. It was found that NeuN/NLRP3-positive cells were increased in animals with a genetic model of Alzheimer's disease in the amygdala (29.052.67) compared with the control animals (17.101.95) (p=0.043). A similar picture was observed in -amyloid-induced neurodegeneration (p=0.021). Intra-hippocampal injection of -amyloid caused the decrease of MAPK expression in the amygdala neurons (5.970.66) compared with sham-operated animals (13.252.65) (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. Wefound a decrease of the expression of MAPK on neurons in the amygdala. This indicates coupling of the inflammatory process and the disturbances of insulin-signaling mechanisms in the brain in neurodegeneration.

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