Investigation of brain creatine levels under the mental stress conditions

Alterations in brain creatine levels are considered to be associated with various pathological conditions. However, there is still no exact evidence on character of this changes and clear link between disorders and upstream and downstream direction of creatine changes. Chronic mental stress conditions are thought to be connected with upstream regulation of cellular oxidative pathways, thus oxidizing various structural and active compounds. Oxidative stress also takes part in increase of permeability of blood brain barrier (BBB) that, in turn, makes it possible for a number of molecules to cross the BBB in both directions. Observations on long-term social isolation and circadian rhythm violation show a rising trend in brain creatine amount, while there was remarkable down-regulation in creatine synthesizing system, as the key-enzymes’ (AGAT and GAMT) activity was decreased. Investigations of BBB permeability for creatine under the stress conditions by mass-spectrometric analyses revealed no changes in creatine transport in the stress group, compared to the control. However, the activity of mitochondrial CK was reduced for about 25% and Vmax had fallen down in the stressed group, the Km was not drastically changed. To sum up, it could be supposed that the reason for the elevations of creatine levels in brain under the mental stress conditions could be stimulated by the activated oxidative stress that induces conformational changes in mitochondrial Creatine Kinase structure and decreasing the ability of enzyme to phosphorylate the creatine and as a result free creatine levels in brain are being arisen.