2021
Volume 21, Number 3, pp. 69-78
The effects of exogenously administered creatine on the PI3-AKT-mTOR signaling pathway during chronic stress conditions
Mariam Shengelia, George Burjanadze, Zurab Kuchukashvili, Natalia Dachanidze, Mariam Mikadze and Nana Koshoridze
Department of Biology, Faculty of Exact and Natural Sciences, Ivane Javakhishvili Tbilisi State University, Georgia
Chronic stress leads to cellular metabolism changes, which diminish the cell's energy status and the intensity of anabolic reactions. Hence, searching for substances that can prevent these processes during stress is important. Our attention was drawn to creatine. It is endogenous in mammals and given as a supplement during strenuous physical exertion and with therapeutic effect in certain neurodegenerative diseases. Our experiments showed that intraperitoneal injections of creatine during prolonged disruption of circadian rhythm activate mitochondrial enzymes involved in energy metabolism in the hippocampus. From investigation of the PI3K-AKT-mTOR pathway under chronic stress and administration of exogenous creatine we inferred that creatine increases the amount of phosphorylated mTOR and its activator AKT, which is initially decreased due to stress, weakening energy metabolism. This inference was strengthened by data on upregulation of PTEN, a negative regulator of AKT. Hence, it is proposed that the diminishing energy metabolism under chronic stress is due to downregulation of the PI3K-AKT-mTOR pathway; exogenous creatine counters the dim-inution by increasing the activity of energy metabolism enzymes, which may be directly related to upregulation of the PI3K-AKT-mTOR pathway.
Keywords: creatine kinase, energy metabolism, hippocampus, psychoemotional stress