New magnetic resonance spectroscopy biomarker for monitoring neurodegenerative diseases: animal models.
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.
Kasparová
Svatava
S
NMR Laboratory, Slovak University of Technology in Bratislava, Slovakia.
Sumbalová
Zuzana
Z
Horecký
Jaromír
J
Bystrický
Peter
P
Mlynárik
Vladimír
V
Gvozdjáková
Anna
A
Liptaj
Tibor
T
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism; D003402:Creatine Kinase / Q000032:analysis*; D015140:Dementia, Vascular / Q000175:diagnosis; D004195:Disease Models, Animal; D004734:Energy Metabolism; D006816:Huntington Disease; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019636:Neurodegenerative Diseases / Q000175:diagnosis*; D051381:Rats
D015415:Biomarkers; D003402:Creatine Kinase