Sleep Deprivation Increases A<sub>1</sub>Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study

Elmenhorst, David; Meyer, Philipp T.; Winz, Oliver; Matusch, Andreas; Neumaier, Bernd; Coenen, Heinz H.; Basheer, Radhika; Haas, Helmut L.; Zilles, Karl; Bauer, Andreas

doi:10.1523/jneurosci.5066-06.2007

Cited by 169 publications

(127 citation statements)

References 29 publications

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“…This fluctuation in adenosine over the sleep-wake cycle has also been observed in the forebrain of animals (Porkka-Heiskanen 1997). Studies have observed both this natural homeostatic oscillation of adenosine as well as an increase in adenosine signaling with extended periods of wakefulness (Porkka-Heiskanen 1997;Basheer et al 2007;Elmenhorst et al 2007). The increase in adenosine after periods of wakefulness contributes to the increased drive for sleep.…”

Section: Adenosine and Astrocytesmentioning

confidence: 63%

The impact of sleep loss on hippocampal function

2013

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Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep deprivation to impair memory consolidation and plasticity. In this review, we address these topics with a focus on the detrimental effects of post-learning sleep deprivation on memory consolidation. Obtaining adequate sleep is challenging in a society that values "work around the clock." Therefore, the development of interventions to combat the negative cognitive effects of sleep deprivation is key. However, there are a limited number of therapeutics that are able to enhance cognition in the face of insufficient sleep. The identification of molecular pathways implicated in the deleterious effects of sleep deprivation on memory could potentially yield new targets for the development of more effective drugs.

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Section: Adenosine and Astrocytesmentioning

confidence: 63%

The impact of sleep loss on hippocampal function

2013

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“…As shown previously, there is a high test-retest reliability of A 1 AR availability after an 8-h sleep episode (29), which is also comparable between groups of the same age (30). Receptor binding data of earlier experiments after 8 h of sleep at night (27,29) were therefore integrated into the present analyses as independent control group values (Table 1).…”

mentioning

confidence: 81%

“…However, positron emission tomography (PET) is a tool that allows for exploring adenosine receptors in vivo. In earlier experiments, we already found evidence that A 1 AR availability is stable after repeated 8-h sleep episodes (29) and increased after 24 h of sleep deprivation (27). In the present study, we intended to increase sleep pressure even further to examine if A 1 AR availability is satiating, as predicted by the two-process model, and whether the exponential discharge of sleep pressure during recovery sleep is reflected in A 1 AR availability.…”

mentioning

confidence: 85%

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Recovery sleep after extended wakefulness restores elevated A ₁ adenosine receptor availability in the human brain

Elmenhorst

Hennecke

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Adenosine and functional A 1 adenosine receptor (A 1 AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A 1 AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [ 18 F]CPFPX positron emission tomography was used to quantify A 1 AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A 1 AR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in A 1 AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A 1 AR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in A 1 AR availability. Sleep deprivation resulted in a higher A 1 AR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in A 1 AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A 1 AR availability might be causal for individual responses to sleep loss.S leep loss is known to impair almost every aspect of cognition, such as learning (1), long-term memory consolidation (2), attention and psychomotor vigilance (PVT) (3), and executive functions (4), including decision making (5) and emotional control (6). Sleep deprivation further typically alters the frequency distribution of the waking electroencephalogram (EEG) as an indicator of alertness corresponding to cognitive performance (7). However, large interindividual differences exist in the degree of cognitive performance decline during sleep deprivation (3). In a trait-like process, some individuals keep high-level performance during sustained wakefulness, whereas others suffer from severe performance loss (3). The neuro-molecular mechanisms in the brain responsible for these different vulnerabilities are still largely unknown. Caffeine, commonly consumed for fighting fatigue, promotes wakefulness via adenosine receptor antagonism. It seems likely that the adenosinergic system is a neurochemical link between performance and sleep (8). Adenosine is contributing to the homeostatic process of sleep-wake regulation (for review, see refs. 9-12). As has been shown in cats and rats, extracellular adenosine concentration fluctuates rhythmically in many brain regions, such as the basal forebrain, increasing during wakefulness and decreasing during sleep: it thereby induces sleep after wake extension and is in turn restored to baseline levels after recovery sleep (13). For additional information on adenosine, see...

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“…Adenosine receptors have been implicated in regulating coronary blood flow and oxygen consumption by cardiac muscle and are present in the brain, most notably in the forebrain [34,35]. CBD (50 μg/kg) inhibits the subsequent ventricular tachycardia following coronary artery occlusion in rats-an effect abolished by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A 1 receptor antagonist (Table 1).…”

Section: Adenosinementioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

447

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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Sleep Deprivation Increases A₁Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study

Cited by 169 publications

References 29 publications

The impact of sleep loss on hippocampal function

The impact of sleep loss on hippocampal function

Recovery sleep after extended wakefulness restores elevated A ₁ adenosine receptor availability in the human brain

Molecular Targets of Cannabidiol in Neurological Disorders

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Sleep Deprivation Increases A1Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study

Cited by 169 publications

References 29 publications

The impact of sleep loss on hippocampal function

The impact of sleep loss on hippocampal function

Recovery sleep after extended wakefulness restores elevated A 1 adenosine receptor availability in the human brain

Molecular Targets of Cannabidiol in Neurological Disorders

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Product

Resources

About

Sleep Deprivation Increases A₁Adenosine Receptor Binding in the Human Brain: A Positron Emission Tomography Study

Recovery sleep after extended wakefulness restores elevated A ₁ adenosine receptor availability in the human brain