Diurnal changes in glutamate/glutamine levels of healthy young adults assessed by proton magnetic resonance spectroscopy

Abstract

Molecular and electrophysiological studies suggest that sleep ensures efficient functioning of the brain by maintaining synaptic homeostasis. The glutamate receptor -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) is involved in synaptic plasticity processes and it was shown that its expression changes across the sleep wake cycle. Moreover, animal studies have shown that glutamate levels are reduced during non-rapid eye movement (NREM) sleep and that the rate of the decrease is positively correlated with sleep EEG slow wave activity (SWA). In this study, we aimed to assess if proton magnetic resonance spectroscopy (1H-MRS) is sensitive to diurnal changes of glutamate + glutamine (GLX) in healthy young adults and if potential overnight changes of GLX are correlated to SWA. 1H-MRS spectra of 16 adult subjects were measured in the parietal lobe in the evening and in the subsequent morning using a 3T MRI scanner. The night between the scans was recorded with high-density EEG. Our results revealed a significant overnight reduction in GLX levels, whereas other metabolites did not show any significant change. Moreover, the decrease in GLX was positively correlated with the decrease of SWA in the course of the night. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of 1H-MRS and indicates a relationship between changes in GLX and SWA, a marker that is closely linked to the restorative function of sleep. This relationship might be of particular interest in clinical populations in which sleep is disturbed.