Because this experiment was a spin-off, we did not have clear a priori hypotheses on concentration changes, nor did we specifically design our experiment for measurements of amino acids. We selected these amino acids as they can be measured in a single UPLC run. In this paper we describe our experiment that investigates the effects of 12h of sleep deprivation on medial PFC (mPFC) concentrations of Hist, asparagine (Asn), Asp, GABA, Glu, glutamine (Gln), Gly, proline (Pro) and Tau, analysing left-over microdialysis sample volume from another experiment. The dialysate is then analysed by ultra-high-pressure liquid chromatography (UPLC). Microdialysis is based on simple diffusion through a semi-permeable membrane from the tissue of interest into a continuously flowing isotonic fluid. Extracellular concentrations present direct information on the activity status of neurotransmitters and neuromodulators in a certain brain region, in contrast to total brain concentrations. Microdialysis is a convenient and elegant method to study extracellular biochemistry over time. GABA (gamma-aminobutyric acid), glycine (Gly) and taurine (Tau)) neurotransmitters and neuromodulators. glutamate (Glu) and aspartate (Asp)) and inhibitory (e.g. Therefore we focus here on 1) Hist, a monoamine that is as important as the other monoamines in the regulation of sleep and wakefulness but is much less studied, and 2) excitatory (e.g. In contrast to monoamines and adenosine, other transmitters that are important in sleep regulation such as the amino acids and histamine (Hist) did not receive much attention. To learn more about the neurobiological mechanisms involved, extracellular concentrations of neurotransmitters have been studied. on tasks addressing working memory and task switching. Besides, prefrontal tasks such as attention, working memory, temporal memory and behavioural inhibition are affected by sleep deprivation in humans, but also in animals, e.g. Prefrontal regions show prominent deactivation during sleep and sleep deprivation. Sleep seems necessary for prefrontal cortex (PFC)-dependent tasks. Further studies are needed for drawing solid conclusions. Sleep deprivation increased glutamate and GABA exclusively in the cortex. Aspartate, glycine, asparagine and taurine were less often studied (1-2 times), but peaked exclusively during sleep. Glu (k = 11) and GABA (k = 8) concentrations in different brain areas were reported to peak during sleep or wakefulness or to lack state-dependency. Histamine was low during sleep, but high during sleep deprivation and wakefulness, irrespective of brain area. We retrieved 13 papers reporting on one or more of the molecules of interest during naturally occurring sleep, 2 during sleep deprivation and 2 during both. For other compounds, no differences were observed between light and dark circadian phase, and between sleep deprivation, recovery and baseline. Glutamine was higher during post-SD recovery than during baseline (p = 0.010). In our experiment, median concentrations of glutamate were higher during SD than during baseline (p = 0.013) and higher during the dark-active than during the resting phase (p = 0.003). Additionally, we systematically reviewed the literature on studies reporting microdialysis measurements relating to sleep throughout the brain. We determined extracellular concentrations of histamine and 8 amino acids in the medial PFC before, during and after SD. Here, we focus on the activity of these molecules in the PFC during sleep and sleep deprivation (SD).
Less attention has been paid to the amino acid transmitters and histamine. The role of different neurotransmitters has been studied, mainly the catecholamines and serotonin. Sleep seems essential to proper functioning of the prefrontal cortex (PFC).
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