Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain

Abstract

In this study, ascorbate (Asc) and glutathione (GSH) concentrations were quantified noninvasively using double-edited (1)H MRS at 4 T in the occipital cortex of healthy young [age (mean ± standard deviation) = 20.4 ± 1.4 years] and elderly (age = 76.6 ± 6.1 years) human subjects. Elderly subjects had a lower GSH concentration than younger subjects (p < 0.05). The Asc concentration was not significantly associated with age. Furthermore, the lactate (Lac) concentration was higher in elderly than young subjects. Lower GSH and higher Lac concentrations are indications of defective protection against oxidative damage and impaired mitochondrial respiration. The extent to which the observed concentration differences could be associated with physiological differences and methodological artifacts is discussed. In conclusion, GSH and Asc concentrations were compared noninvasively for the first time in young vs elderly subjects.

Copyright © 2011 John Wiley & Sons, Ltd.

Figures

Figure 1

Representative double editing with MEGA-point-resolved spectroscopy (DEW MEGA-PRESS) spectra (TE = 122 ms; TR = 4.5 s; number of excitations = 512) from one young (left) and one elderly (right) subject. Constancy or differences in ascorbate (Asc) (3.73 ppm), glutathione (GSH) (2.95 ppm) and lactate (Lac) (1.33 ppm) resonances are illustrated with horizontal broken lines. Gaussian filtering with σ = 0.15 s was applied. Spectra are scaled such that the heights of the Asc peaks are equal. The zero level is indicated by a gray horizontal line. Top: transverse MRI illustrating (box) the location of the volume of interest in the occipital lobe. GPE, glycerophosphorylethanolamine; Ins, myo-inositol; NAA, N-acetylaspartate.

Figure 2

A representative result of quantification via LCModel. In vivo: edited spectrum. LCModel: overall fit of the edited spectrum; fitted components for ascorbate (Asc), glutathione (GSH), N-acetylaspartate (NAA), lactate (Lac), myo-inositol (Ins), phosphorylcholine (PC), phosphorylethanolamine (PE), glycerophosphorylcholine (GPC) and glycerophosphorylethanolamine (GPE); baseline component of LCModel fitting and fitted residual.

Figure 3

Concentrations of ascorbate (Asc) (top), glutathione (GSH) (middle) and lactate (Lac) (bottom) by age group, together with means (boxes) and standard deviations (error bars). Concentrations were quantified in institutional units (i.u.) which were designed to estimate the concentration (µmol/g wet weight) without correction for T2. Means and standard deviations of the concentrations were intentionally shifted to the left of the mean age of each group for clarity.

Figure 4

The voxel fraction of cerebrospinal fluid (fCSF) by age group, together with means (boxes) and standard deviations (error bars). fCSF was significantly higher in elderly subjects (p < 0.05). Means and standard deviations of fCSF were intentionally shifted to the left of the mean age of each group for clarity.