Stress caused by circadian rhythm disruption and possible preventive action of creatine

Disruption of the natural circadian rhythm leads to changes in cellular metabolism and the creation of a stressful environment for the body, which is manifested by a significant decrease in synthetic and energetic reactions. There are many compounds that are used to prevent damage during stressful situations. For this purpose, creatine turned out to be interesting compound for us, given that the latter is an endogenous substance. Creatine has an important role in metabolism and is also used as a therapeutic agent for a number of neurodegenerative diseases. It is known that, exogenous supply of creatine in conditions of prolonged circadian rhythm disturbances promotes the activation of enzymes involved in energy processes in hippocampal cells. Our research has shown that the main reason for this is the activation of synthesis reactions. The central signaling molecule in the regulation of energetical metabolism is mTOR. We have studied the quantitative changes in mTOR under conditions of prolonged circadian rhythm disturbances and the effect of creatine on this process. Exogenous supply of creatine increases the amount of phosphorylated mTOR and its activator-AKT which decreases during stress, developed as a result of prolonged circadian rhythms. At the same time, activation of PTEN, a negative regulator of AKT, is observed during stress. Based on our studies, it has been suggested that PTEN activation and decreased amount of mTOR and AKT during stress due to circadian rhythm disturbances may be a result of NMDA-receptor hyperactivity in brain hippocampal cells, resulting in an increase in the amount of CA2+ ions in the hippocampus. It has been suggested that the positive role of creatine is due to its modulatory effect on the NMDA receptor, which reduces the amount of intracellular Ca2+.

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