Brain Microdialysate Monoamines in Relation to Circadian Rhythms, Sleep, and Sleep Deprivation – a Systematic Review, Network Meta-analysis, and New Primary Data

Abstract

Disruption of the monoaminergic system, e.g. by sleep deprivation (SD), seems to promote certain diseases. Assessment of monoamine levels over the circadian cycle, during different sleep stages and during SD is instrumental to understand the molecular dynamics during and after SD. To provide a complete overview of all available evidence, we performed a systematic review. A comprehensive search was performed for microdialysis and certain monoamines (dopamine, serotonin, noradrenaline, adrenaline), certain monoamine metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA)) and a precursor (5-hydroxytryptophan (5-HTP)) in PubMed and EMBASE. After screening of the search results by two independent reviewers, 94 publications were included. All results were tabulated and described qualitatively. Network-meta analyses (NMAs) were performed to compare noradrenaline and serotonin concentrations between sleep stages. We further present experimental monoamine data from the medial prefrontal cortical (mPFC). Monoamine levels varied with brain region and circadian cycle. During sleep, monoamine levels generally decreased compared to wake. These qualitative observations were supported by the NMAs: noradrenaline and serotonin levels decreased from wakefulness to slow wave sleep and decreased further during Rapid Eye Movement sleep. In contrast, monoamine levels generally increased during SD, and sometimes remained high even during subsequent recovery. Decreases during or after SD were only reported for serotonin. In our experiment, SD did not affect any of the mPFC monoamine levels. Concluding, monoamine levels vary over the light-dark cycle and between sleep stages. SD modifies the patterns, with effects sometimes lasting beyond the SD period.

Shank3 modulates sleep and expression of circadian transcription factors

“…Shank3 ∆C mice were reported to have deficits in motor coordination (Kouser et al, 2013); however, under a 12:12 hr LD schedule their wheel-running activity increases over time (Supplementary file 1, Source data 1). Daily rhythms of activity in rodents are linked to circadian oscillations in dopamine release (Feenstra et al, 2000; Menon et al, 2019) in the frontal cortex as well as in the striatum, a motor region with high levels of Shank3 expression (Peça et al, 2011). Together with a reduction in circadian gene expression, this DD-specific activity deficit suggests that the mutant sleep phenotype involves clock gene functions outside of their central time-keeping role.…”

Hippocampal 2-Arachidonoyl Glycerol Signaling Regulates Time-of-Day- and Stress-Dependent Effects on Rat Short-Term Memory

“…Similar to corticosterone, activity of arousal system mediators is also influenced by circadian rhythm, with norepinephrine reaching its peak at the onset of the dark phase [ 40 ].…”

Disrupted Sleep and Circadian Rhythms in Schizophrenia and Their Interaction With Dopamine Signaling

“…Several elements of DA signaling have a diurnal rhythm, including expression of DA receptors and tyrosine hydroxylase (TH), the rate-limiting enzyme in DA synthesis (Castañeda et al, 2004;Weber et al, 2004;Ferris et al, 2014;Ozburn et al, 2015;Sidor et al, 2015). Numerous rodent studies have reported diurnal changes in extracellular DA levels in various brain regions such as the prefrontal cortex and nucleus accumbens, with generally higher levels at night when rodents are active (Smith et al, 1992;Hood et al, 2010;Menon et al, 2019). Similarly, circulating DA levels in men peak during the day (Sowers and Vlachakis, 1984).…”

“…There are also changes in extracellular DA levels across the spontaneous sleep/wake cycle. The fluctuations vary between brain regions, but generally levels are higher during wakefulness (Léna et al, 2005;Dong et al, 2019;Menon et al, 2019). In the mouse striatum, DA levels also exhibit dynamic changes within periods of wakefulness and at sleep/wake state transitions (Dong et al, 2019).…”