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

Abstract

The glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is involved in synaptic plasticity processes, and animal studies have demonstrated altered expression across the sleep wake cycle. Accordingly, glutamate levels are reduced during non-rapid eye movement (NREM) sleep and the rate of this decrease is positively correlated with sleep EEG slow wave activity (SWA). Here, we combined proton magnetic resonance spectroscopy ( H-MRS) and high-density sleep EEG to assess if H-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. H-MRS was measured in the parietal lobe in the evening and in the subsequent morning. High-density sleep EEG was recorded overnight between the evening and morning scans. Our results revealed a significant overnight reduction in GLX, but no significant changes in other metabolites. The decrease in GLX positively correlated with the decrease of SWA. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of H-MRS and indicates that overnight changes in GLX are related to 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.

Effect of acute total sleep deprivation on plasma melatonin, cortisol and metabolite rhythms in females

“…These results can be attributed to increased energy demands and increased need for removal of metabolic waste products from the brain during sleep deprivation (Xie et al., ). Diurnal changes in brain glutamate and glutamine levels were recently observed in healthy young adults with a significant overnight reduction assessed by proton magnetic resonance spectroscopy (Volk, Jaramillo, Merki, O'Gorman Tuura, & Huber, ). In addition, a previous study reported reduced glutamine levels associated with lower total sleep time and increased wake‐time after sleep onset (Miller et al., ), supporting our hypothesis.…”

Dynamic changes in cerebral and peripheral markers of glutamatergic signaling across the human sleep–wake cycle

“…Methodological advances in 1 H-MRS have recently permitted the noninvasive detection of naturally occurring changes in tightly regulated metabolite concentrations in circumscribed areas of the human brain. Whereas one recent study suggested that GLX levels in the left parietal lobe decrease overnight [45], previous data from this lab revealed no significant changes after sleep deprivation in GLX/Glu and GABA in the medial prefrontal cortex [17]. Thus, the exact roles in humans of the main excitatory and inhibitory neurotransmitters in circadian and homeostatic sleep–wake regulation remain unclear.…”

Diurnal variability of cerebral metabolites in healthy human brain with 2D localized correlation spectroscopy (2D L‐COSY)

“…Structures such as medial the temporal lobe, prefrontal cortex, and posterior cingulate cortex are prone to diurnal fluctuations at the neuronal activity level . At the metabolic level, diurnal variations of major metabolites such as NAA, tCr, Glx, and GABA have been previously investigated using single‐voxel spectroscopic methods, with mixed outcomes. Soreni et al in 2006 found a statistically significant increase in NAA but not with creatine levels on the striatum in the morning .…”

“…Soreni et al found significantly higher levels of NAA during afternoon sessions in a group of healthy controls, which they claim is due to possible changes in circadian mediators such as temperature, hydration, and osmotic regulation . In contrast, Volk et al observed a significant overnight reduction in Glx, whereas other metabolites were not affected by the circadian change . Other studies, on the other hand, showed that the time of day had no bearing on metabolic concentrations, in particular, GABA and other major metabolites such as NAA and creatine .…”