Reduced creatine kinase B activity in multiple sclerosis normal appearing white matter

• Published in: PloS one 2010-05, Vol.5 (5), p.e10811-e10811
• Main Authors: Steen, Christel, Wilczak, Nadine, Hoogduin, Johannes M, Koch, Marcus, De Keyser, Jacques
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Adenosine Triphosphate - metabolism; Amino acids; Aspartic Acid - analogs & derivatives; Aspartic Acid - metabolism; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Axons; Benign; Brain - enzymology; Brain - pathology; Case-Control Studies; Central nervous system; Comparative analysis; Creatine; Creatine kinase; Creatine Kinase, BB Form - metabolism; Degeneration; Disease control; Enzyme-linked immunosorbent assay; Female; Gangrene; Humans; Hypoxia; Magnetic resonance; Magnetic Resonance Spectroscopy; Male; Metabolism; Middle Aged; Mitochondria; Models, Biological; Multiple sclerosis; Multiple Sclerosis - enzymology; Multiple Sclerosis - pathology; N-Acetylaspartate; Neurological Disorders; Neurological Disorders/Multiple Sclerosis and Related Disorders; Neurology; Neuroscience/Neuronal and Glial Cell Biology; Nuclear magnetic resonance spectroscopy; Oligodendrocytes; Phosphocreatine; Phosphocreatine - metabolism; Physiological aspects; Postmortem Changes; Rodents; Spectroscopy; Spectrum analysis; Spinal cord; Studies; Substantia alba
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0010811

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. 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