Reduced creatine kinase B activity in multiple sclerosis normal appearing white matter.
BACKGROUND
Two studies using (31)P-magnetic resonance spectroscopy (MRS) reported enhanced phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of subjects with multiple sclerosis (MS), but this finding could not be properly explained.


RESULTS
We performed (31)P-MRS and (1)H-MRS in the NAWM in 36 subjects, including 17 with progressive MS, 9 with benign MS, and 10 healthy controls. Compared to controls, PCr/beta-ATP and PCr/total (31)P ratios were significantly increased in subjects with progressive MS, but not with benign MS. There was no correlation between PCr ratios and the N-acetylaspartate/creatine ratio, suggesting that elevated PCr levels in NAWM were not secondary to axonal loss. In the central nervous system, PCr is degraded by creatine kinase B (CK-B), which in the white matter is confined to astrocytes. In homogenates of NAWM from 10 subjects with progressive MS and 10 controls without central nervous system disease, we measured CK-B levels with an ELISA, and measured its activity with an enzymatic assay kit. Compared to controls, both CK-B levels and activity were decreased in subjects with MS (22.41 versus 46.28 microg/ml; p = 0.0007, and 2.89 versus 7.76 U/l; p<0.0001).


CONCLUSIONS
Our results suggest that PCr metabolism in the NAWM in MS is impaired due to decreased CK-B levels. Our findings raise the possibility that a defective PCr metabolism in astrocytes might contribute to the degeneration of oligodendrocytes and axons in MS.
Department of Neurology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Christel
C
Steen
Nadine
N
Wilczak
Johannes M
JM
Hoogduin
Marcus
M
Koch
Jacques
J
De Keyser
D000255:Adenosine Triphosphate / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology*; D016022:Case-Control Studies; D052276:Creatine Kinase, BB Form / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000473:pathology*; D010725:Phosphocreatine / Q000378:metabolism; D011180:Postmortem Changes
D010725:Phosphocreatine; D001224:Aspartic Acid; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D052276:Creatine Kinase, BB Form