Investigation of Molecular Basis of Creatine-facilitated Prevention of Brain Energy Metabolism under the Chronic Stress

Author: nino papelishvili
Keywords: stress, circadian rhythm, creatine
Annotation:

It is well known that disruption of natural Circadian Rhythm lead to changes in the cellular metabolism and development of chronic stress, which involves reduction in the energetic status of individual cells, as well as, intensity of synthetic reactions. Considering the above mentioned, it is crucial to discover substances that can prevent the development of these processes during stressful conditions. Our attention was drawn to Creatine. It is an endogenous substance in the mammals, used as a supplement during strenuous physical exertion and also used as a therapeutic means for certain neurodegenerative diseases. The conducted experiments showed that intraperitoneal injections of Creatine during prolonged disruption of Circadian Rhythm, assist in activation of Mitochondrial enzymes involved in energy metabolism in Hippocampal cells. Since, central regulatory substance in processes of energy metabolism is signaling molecule, mTOR, we studied its quantitative changes during prolonged disruption of Circadian Rhythm and influence of exogenous Creatine. The results revealed that exogenous supplementation of Creatine increases the amount of phosphorylated mTOR, as well as its activator – AKT, which were originally decreased as a result of stress conditions and express weakened energy metabolism processes. This assumption is also confirmed by our data, which show the activation of negative regulator of AKT, PTEN. Thus, we hypothesize based on this, as well as, our past results that activation of PTEN and consequently, reduction in the activities of AKT and mTOR in Hippocampal cells during stress conditions caused by disruption of Circadian Rhythm, are the result of hyperactivation of NMDA receptors, which led to increased concentration of Ca2+. Consequently, it can be assumed that the positive role of Creatine on these processes is exerted via its modulatory effects on NMDA receptors that causes lowering of Ca2+ concentration and thus, lowering of PTEN activation, which increases quantity of activated AKT, as well as, activated mTOR.