Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T.
Histopathological reports of multiple sclerosis and its animal models have shown evidence of a link between axonal injury in active lesions and impaired glutamate metabolism. Mature oligodendrocytes play a role in glutamate uptake to maintain glutamate homeostasis but in multiple sclerosis white matter the loss of expression of glutamate transporters in the lesion vicinity results in ineffective glutamate removal. Using a magnetic resonance spectroscopy technique that isolates the glutamate resonance at 3 T, we compared glutamate levels between normal subjects and multiple sclerosis patients in different brain areas. Metabolite concentrations (glutamate, glutamine, N-acetyl-aspartate, myo-inositol, choline, creatine) were derived from LCmodel and corrected for T1 relaxation time. Glutamate concentrations were found to be elevated in acute lesions (P = 0.02) and normal-appearing white matter (P = 0.03), with no significant elevation in chronic lesions (P = 0.77). The N-acetyl-aspartate level in chronic lesions was significantly lower (P < 0.001) than in acute lesions and normal-appearing white matter. The choline level in acute lesions was significantly higher (P < 0.001) than in chronic lesions. Evidence was also found for increased glial activity in multiple sclerosis, with significantly higher (P < 0.001) myo-inositol levels in acute lesions compared with control white matter. These in vivo results support the hypothesis that altered glutamate metabolism is present in brains of multiple sclerosis patients.
Srinivasan
Radhika
R
Center for Molecular and Functional Imaging, Department of Radiology, University of California-San Francisco, 185 Berry Street, #350, San Francisco, CA 94107-1739, USA. rsriniva@mrsc.ucsf.edu
Sailasuta
Napapon
N
Hurd
Ralph
R
Nelson
Sarah
S
Pelletier
Daniel
D
D000208:Acute Disease; D000328:Adult; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*
D018698:Glutamic Acid; D007294:Inositol; D002794:Choline