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

Area of Science:

• Neuroscience
• Biochemistry
• Magnetic Resonance Spectroscopy

Background:

• Previous studies using 31P-magnetic resonance spectroscopy (MRS) reported elevated phosphocreatine (PCr) levels in normal appearing white matter (NAWM) of multiple sclerosis (MS) patients.
• The underlying reasons for these enhanced PCr levels in MS NAWM remained unexplained.

Purpose of the Study:

• To investigate the cause of elevated PCr levels in NAWM in MS.
• To examine the role of creatine kinase B (CK-B) in PCr metabolism in MS NAWM.

Main Methods:

• Performed 31P-MRS and 1H-MRS on 36 subjects (17 progressive MS, 9 benign MS, 10 controls).
• Measured CK-B levels and activity in NAWM homogenates from 10 progressive MS patients and 10 controls using ELISA and enzymatic assay kits.

Main Results:

• Progressive MS patients showed significantly increased PCr/beta-ATP and PCr/total 31P ratios in NAWM compared to controls.
• No correlation was found between PCr ratios and N-acetylaspartate/creatine ratio, suggesting elevated PCr is not due to axonal loss.
• Both CK-B levels and activity were significantly decreased in NAWM of MS patients compared to controls.

Conclusions:

• Impaired PCr metabolism in MS NAWM is likely due to decreased CK-B levels.
• Defective PCr metabolism in astrocytes may contribute to oligodendrocyte and axon degeneration in MS.