A Systematic Search and Mapping Review of Studies on Intracerebral Microdialysis of Amino Acids, and Systematized Review of Studies on Circadian Rhythms

Abstract

Background:Microdialysis can be used to measure amino acids in the extracellular space in vivo, based on the principle of diffusion. Variations in experimental set-up result in variations in baseline levels of the compounds measured. Variations may also be due to circadian rhythms.Method:We systematically searched and mapped the literature on all studies reporting baseline microdialysis measurements of histamine and the amino acids asparagine, aspartate, GABA, glutamate, glutamine, glycine, proline and taurine. We fully reviewed the studies describing circadian rhythms for histamine and the selected amino acids.Results:We retrieved 2331 papers describing baseline measurements of one or more of the compounds of interest. We provide a numerical summary and lists of the publications by compound. We retrieved 11 references describing studies on the circadian rhythms of the compounds of interest. Aspartate, glutamate and histamine are generally higher during the dark than during the light phase in nocturnal rodents. For glutamine, no rhythmicity was observed. For GABA, the results were too inconsistent to generalise. For asparagine, glycine, proline and taurine, insufficient data are available.Conclusion:The literature on intracerebral microdialysis measurements of the amino acids is vast, but certain primary studies are still warranted. Future systematic reviews on the individual compounds can shed light on the effects of experimental variations on baseline concentrations.

Circadian-Like Rhythmicity of Extracellular Brain Glutamate in Epilepsy

“…The novel finding of this study is that extracellular glutamate exhibits 24-h concentration changes in the seizure onset area in a model of MTLE. While other investigators have described 24-h oscillations of glutamate in the suprachiasmatic nucleus, the nucleus accumbens, and the striatum (15), this is the first demonstration of such changes in an epileptogenic region of the brain. hippocampi.…”

“…For example, the patterns of seizure periodicity are highly variable, making it difficult to implement a "one size fits all" therapeutic approach. This variability may be caused by the combined effects of several factors such as the expression of circadian core genes (12), day/night patterns (13), sleep wake cycles (14), location of the seizure onset area, and intrinsic metabolic rhythms (15). Understanding the mechanisms underlying seizure periodicity is important as it may allow more precise and effective approaches which can be tailored to each patient.…”

“…The excitatory neurotransmitter glutamate is an essential modulator of circadian rhythms (16), and studies have shown that extracellular glutamate levels fluctuate during the circadian cycle in the suprachiasmatic nucleus, striatum, and nucleus accumbens of rats (15). Moreover, the circadian changes in extracellular glutamate levels are likely driven by astrocytes and may play a role in the circadian timekeeping of the suprachiasmatic nucleus (17).…”

Sleep and Microdialysis: An Experiment and a Systematic Review of Histamine and Several Amino Acids

“…We previously published a systematic mapping review on Hist and the amino acids Asn, Asp, GABA, Glu, Gln, Gly, Pro and Tau as assessed by intracerebral microdialysis [17]. In this SR, we followed the same methodology up to the selection of papers.…”

“…Discrepancies were resolved by discussion among the reviewers. For our mapping review [17], we excluded (1) studies on other techniques than microdialysis (e.g. biosensors and microdialysis precursors such as push-pull perfusion), (2) studies measuring other substances than Hist and the amino acids Asn, Asp, GABA, Glu, Gln, Gly, Pro and Tau, (3) retro-dialysis studies, (4) microdialysis studies that did not report baseline values without the specified molecules in the perfusion fluid, (5) extra-cerebral microdialysis studies, (6) human and in vitro studies, and (7) papers not containing primary study data.…”