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

19Citations
Citations of this article
34Readers
Mendeley users who have this article in their library.

Abstract

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

Cite

CITATION STYLE

APA

Steen, C., Wilczak, N., Hoogduin, J. M., Koch, M., & de Keyser, J. (2010). Reduced creatine kinase B activity in multiple sclerosis normal appearing white matter. PLoS ONE, 5(5). https://doi.org/10.1371/journal.pone.0010811

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free