STRESS-AFFECTED AKT/MTOR PATHWAY UPREGULATED BY LONG-TERM CREATINE INTRAPERITONEAL ADMINISTRATION.

Disruption of natural circadian rhythm leads to the development of chronic stress. It provokes cellular metabolism changes, including a reduction in energy production and downregulation of anabolic reaction. Considering the importance of those processes, it is crucial discovering the substances that can prevent those stress-induced alterations. Our attention was drawn to Creatine. The experiments showed that Creatine's intraperitoneal injections during a prolonged disruption of circadian rhythm help activate mitochondrial creatine kinase. Since the central regulatory substance in energy metabolism is the signalling molecule mTOR, we studied its quantitative changes under long-term disruption of circadian rhythm and exogenous creatine administration. The results revealed that Creatine's exogenous supplementation increases phosphorylated mTOR and its activator - Akt. Consequently, it can be assumed that Creatine performs its positive role in hippocampal cells' energy metabolism via its modulatory effects on the PI3K/Akt/mTOR signalling pathway.