Role of glycogene synthase kinase in brain insulin resistance in a model of neurodegenerative disease
Abstract
Diabetes mellitus (DM) and neurodegenerative processes have a number of common features: progression with aging, metabolic disorders, changes in blood vessels, oxidative stress, inflammation, accumulation of advanced glycation end products, insulin resistance, formation of amyloid protein aggregates, increased activity of glycogen synthase kinase (GSK-3 β), dysregulation of tau protein phosphorylation, etc. T2DM or prediabetes affects about 85% of patients with Alzheimer's disease and more than 50% of patients with Parkinson's disease. It is known that GSK3β is not only an important regulator of glucose levels, but also influences the formation of beta-amyloid protein aggregates and the hyperphosphorylation of tau protein. To clarify the contribution of glycogen synthase kinase-3β in the development of insulin resistance, experiments were conducted to determine the level of GSK3β in individual sections of brain tissue from rats with a model of neurodegenerative disease (NDD). Materials and methods An animal model of a sporadic neurodegenerative disease was reproduced using a high-calorie, atherogenic diet and injection of a neurotoxin into the central nervous system. The content of GSK3β in various rat brain sections before and after reproduction of the NDD model was determined by immunoprecipitation with polyclonal antibodies using rabbit antibodies conjugated to horseradish peroxidase. Results were quantified using Scion Image in terms of average signal intensity. Results and discussion The results of the study showed that in hippocampal slices the level of GSK3β changes slightly, with a tendency to decrease. In sections of the striatom, when animals were kept on a high-calorie diet before the administration of streptozocin, GSK3β increases by 10%, and after the administration of the neurotoxin - by 19%. In the olfactory bulb (OВ), GSK3β expression increases with a high-calorie diet by 15% and by 23% after neurotoxin administration. Thus, it should be noted that changes in the expression of glycogen synthase kinase-3β in sections of the striatum and OB of animals under the influence of a high-calorie atherogenic diet and after administration of streptozocin may be one of the main reasons that causes insulin resistance and, as a consequence, the occurrence of a neurodegenerative condition in reproduction of the experimental model of NDZ. Funding: by Mininnovation.uz and WorldBANK ФЗ-2020092959 (Ф-ОТ-2021-153) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.