New Magnetic Resonance Spectroscopy Biomarker for Monitoring Neurodegenerative Diseases: Animal Models

Abstract

Creatine kinase (CK) plays a central role in energy transfer in cells with high-energy demands, and the enzyme is rather susceptible to oxidative inactivation. The aim of the present study was to investigate whether the rate constant of forward CK reaction (k for ) is a suitable indicator of alterations in cerebral energy metabolism. We monitored k for in the rat brain non-invasively by in vivo phosphorus ( 31 P) magnetic resonance spectroscopy (MRS). To alter energy metabolism, we applied following experimental models: Huntington's disease, diabetes mellitus, chronic alcohol intoxication and chronic cerebral hypoperfusion (vascular dementia model). Results of our 31 P MRS experiment confirm importance of creatine kinase/phosphocreatinine (CK/PCr) system in the regulation of brain energy metabolism in vivo because a kinetic parameter k for was significantly changed in all above animal models that simulate neurodegenerative diseases or commonly during oxidative stress. Using this method we distinguished vascular dementia (VD) and Huntington disease (HD), because in VD model a kinetic parameter k for decreased and in the case HD increased. Considering the importance of CK for the maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity in the brain may be one of the mechanisms by which various neurodegenerative diseases might be monitored just by means saturation transfer method 31 P MRS.

Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression

“…36 Furthermore, the rate at which CK catalyzes the PCr to ATP reaction in the brain has been found to be decreased in animal models of altered energy metabolism and neurodegenerative diseases, including diabetes mellitus, Huntington disease, and vascular dementia. 11 …”

Age‐related changes in brain energetics and phospholipid metabolism

“…Creatine kinase plays a critical role in maintaining energy homeostasis and is particularly crucial in tissues with high and fluctuating energy demands such as muscle and brain (31). Situations of a compromised cellular energy state, such as oxidative stress, calcium overload and ischemia that lead to free radical damage, may directly alter the activity and efficiency of the forward rate constant of CK (31,32). Furthermore, modifications of brain CK structure and activity have been demonstrated in studies of neuropsychiatric conditions, including Alzheimer's Dementia (33).…”

31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression

“…CK plays a primary role in maintaining energy homeostasis, particularly in tissues with high and fluctuating energy demands such as muscle and brain (Schlattner et al, 2006). Situations of a compromised cellular energy state, such as oxidative stress, calcium overload and ischemia that lead to free radical damage, may directly alter the activity and efficiency of the forward rate constant of CK (Kasparova et al, 2005;Schlattner et al, 2006). CK catalyzes the CK reaction (PCr þ H þ þ ADP !…”