Open AccessInsulin gene expression and functional activity of insulin signaling pathway in Alzheimer's disease
Author(s) -
Yana V. Gorina,
Е. Д. Хилажева,
Yu. K. Kоmleva,
Olga Lopatina,
Alla Salmina
Publication year - 2021
Publication title -
fundamentalʹnaâ i kliničeskaâ medicina
Language(s) - English
Resource type - Journals
eISSN - 2542-0941
pISSN - 2500-0764
DOI - 10.23946/2500-0764-2021-6-4-8-21
Subject(s) - neurodegeneration , endocrinology , medicine , insulin degrading enzyme , insulin , insulin receptor , amyloid precursor protein , alzheimer's disease , gene expression , hippocampus , hippocampal formation , biology , chemistry , biochemistry , gene , insulin resistance , disease
Aim. To study the insulin (INS) gene expression, insulin and lactate levels, expression of Fe65 adapter protein, and level of oxidative DNA damage marker γH2AX in different brain areas in the experimental model of Alzheimer's disease. Materials and Methods. Male, 4-month-old C57BL/6 mice received either intrahippocampal injection of β-amyloid (C57BL/6 + Aβ 1-42) or phosphate-buffered saline (C57BL/6 + PBS). Insulin (INS) gene expression in the hippocampus and amygdala was assessed by means of reverse transcription-polymerase chain reaction. Levels of lactate and insulin in different brain areas were measured by enzyme-linked immunosorbent assay. Expression of Fe65 adapter protein and γH2AX in the hippocampus was studied by immunofluorescence staining followed by confocal microscopy. Results. We found an overexpression of the INS gene in the hippocampus and amygdala, an increase in lactate level in the hippocampus, and slightly increased insulin level in the amygdala of mice with Alzheimer's disease as compared with the control group. Neurodegeneration was accompanied by an elevated endothelial expression of Fe65 adapter protein (p= 0.04) and γH2AX in hippocampal neurons (p = 0.04). Conclusion. Alzheimer's disease neurodegeneration is accompanied by a disrupted insulin signaling and impaired glucose metabolism in the hippocampus and amygdala. This further leads to a neuronal accumulation of γH2AX and impaired amyloid precursor protein proteolysis because of insulin inability to inhibit its interaction with the Fe65 adapter protein and to prevent formation and deposition of β-amyloid.