Adenosine and Sleep Homeostasis in the Basal Forebrain

Blanco-Centurión, Carlos; Xu, Man; Murillo-Rodrı́guez, Eric; Gerashchenko, Dmitry; Shiromani, Anjelica; Salín-Pascual, Rafael J.; Hof, Patrick R.; Shiromani, Priyattam J.

doi:10.1523/jneurosci.2181-06.2006

Cited by 186 publications

(122 citation statements)

References 59 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Experiment 2: effects of SR141716A, URB597 or VDM-11 on neurochemical levels during the sleep rebound after 6 h of prolonged waking It is widely known that prolonged waking induces endogenous accumulation of several neurochemicals such as monoamines and purines whereas during the sleep rebound period, the contents of these molecules are decreased (Porkka-Heiskanen et al, 2000, 2002Lena et al, 2005;Blanco-Centurion et al, 2006;Monti and Jantos, 2008;Mohammed et al, 2011;Brown et al, 2012). Thus, the rationale of the following experiment was based to test whether SR141716A, URB597 or VDM-11 would modulate the extracellular contents of DA, NE, EP, 5-HT or AD after prolonged waking.…”

Section: Resultsmentioning

confidence: 99%

“…Third, previous reports have shown that SR141716A enhances NE contents (Tzavara et al, 2001(Tzavara et al, , 2003Bedse et al, 2015). Fourth, there is evidence regarding the interaction between the CB 1 cannabinoid receptor and AD system Cerri et al, 2014) suggesting that SR141716A would be blocking the CB 1 cannabinoid receptors present in cholinergic neurons which are placed in basal forebrain, and they are presumably responsible for AD release (Blanco-Centurion et al, 2006;Huang et al, 2011).Taken together, it might be reasonable to consider that SR141716A or URB597 might activate the wake-related neurotransmission systems and control sleep homeostasis. Nevertheless, further studies are needed to clarify whether the endocannabinoid system interacts with wake-related components to control sleep homeostasis.…”

Section: Discussionmentioning

confidence: 95%

“…To obtain the recovery rate, data were calculated as follows: Recovery rate (%) = (the peak area ratio of the sample from microdialysis sample)/(the peak area ratio of the sample in the test solution). Further details of microdialysis procedures are available in previous reports (PorkkaHeiskanen et al, 2000;Blanco-Centurion et al, 2006;Murillo-Rodrı´guez et al, 2007, 2011Mijangos-Moreno et al, 2014.…”

Section: Microdialysismentioning

confidence: 99%

See 2 more Smart Citations

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

View full text Add to dashboard Cite

Abstract-The endocannabinoid system comprises receptors (CB 1 and CB 2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB 1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20 mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB 1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking. Ó

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: Microdialysismentioning

confidence: 99%

See 1 more Smart Citation

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…However, the anatomical focus of these studies has been the BF rather than the cerebral cortex. Extracellular adenosine is known to accumulate in the BF with prolonged wakefulness (39,40). Prolonged waking activates inducible NOS in the BF which can cause adenosine release and thereby facilitate sleep (37).…”

Section: Discussionmentioning

confidence: 99%

Identification of a population of sleep-active cerebral cortex neurons

Gerashchenko

Wisor

Burns

et al. 2008

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

182

162

View full text Add to dashboard Cite

The presence of large-amplitude, slow waves in the EEG is a primary characteristic that distinguishes cerebral activity during sleep from that which occurs during wakefulness. Although sleepactive neurons have been identified in other brain areas, neurons that are specifically activated during slow-wave sleep have not previously been described in the cerebral cortex. We have identified a population of cells in the cortex that is activated during sleep in three mammalian species. These cortical neurons are a subset of GABAergic interneurons that express neuronal NOS (nNOS). Because Fos expression in these sleep-active, nNOS-immunoreactive (nNOS-ir) neurons parallels changes in the intensity of slow-wave activity in the EEG, and these neurons are innvervated by neurotransmitter systems previously implicated in sleep/wake control, cortical nNOS-ir neurons may be part of the neurobiological substrate that underlies homeostatic sleep regulation.Fos ͉ interneuron ͉ neuronal NOS ͉ sleep deprivation ͉ wakefulness S leep is well known to have recuperative properties (1) and to facilitate performance of learned behaviors (2, 3); conversely, sleep deprivation results in cognitive and performance deficits (4). The presence of large-amplitude, slow waves in the EEG is the hallmark that distinguishes cerebral activity during sleep from wakefulness. Because the intensity of slow waves measured in the delta range of the EEG (1.0-4.0 Hz) appears to be homeostatically regulated and proportional to prior wake duration (5), slow-wave activity (SWA) has been hypothesized to be associated with the restorative function of sleep and with synaptic plasticity (2, 3, 6).The neural circuitry underlying SWA involves a corticothalamocortical loop and interplay between a hyperpolarizationactivated cation current (I h ) and a low-threshold Ca 2ϩ current (I t ) in thalamocortical neurons (7,8). It is currently unknown whether the cerebral cortex is an active participant or simply a passive conveyor of sleep history-dependent SWA dynamics. Identification of a discrete sleep-active population of cortical neurons, such as those in the basal forebrain (BF) (9) and the preoptic-anterior hypothalamus (POAH) (10-13), would help distinguish between these alternatives.In experiments conducted in three mammalian species, we found that GABAergic interneurons expressing the enzyme neuronal NOS (nNOS) are activated both during spontaneous sleep and during recovery sleep (RS) after sleep deprivation (SD). The proportion of nNOS-immunoreactive (nNOS-ir) neurons that are activated during sleep is correlated with a measure of SWA intensity known as ''delta energy' ' (14, 15). Because sleep-active, nNOS-ir neurons are innervated by neurotransmitter systems previously implicated in sleep/wake control, cortical nNOS-ir neurons may be a previously unrecognized cell type involved in SWA and part of the neurobiological substrate that underlies homeostatic sleep regulation. Results Fos Expression Is Increased in Cortical nNOS Neurons During RS.Fos expression has previ...

show abstract

“…Hence, to obtain direct data on the sleepiness of experimental rats, a unique rodent multiple sleep latency test (MSLT) was used that contained features of the clinical MSLT and of procedures used in published animal studies (Shiromani et al, 1991;Veasey et al, 2004;Blanco-Centurion et al, 2006). The rodent MSLT was performed in the recovery period following 6 h SI with treadmill off at the beginning of the dark period (N=8); 6 h SI with treadmill off 3 h before the end of the light period (N=8); and 24 h SI (N=8).…”

Section: Rodent Multiple Sleep Latency Test Following Si Exposuresmentioning

confidence: 99%

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness

et al. 2007

View full text Add to dashboard Cite

Sleep fragmentation, a feature of sleep apnea as well as other sleep and medical/psychiatric disorders, is thought to lead to excessive daytime sleepiness. A rodent model of sleep fragmentation was developed (termed sleep interruption, SI), where rats were awakened every 2 min by the movement of an automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats exposed to 24h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total REM sleep time was greatly reduced, NREM sleep episode duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the total amount of NREM sleep time per 24h approached basal levels. Both 6 and 24 h of SI made rats more sleepy, as indicated by a reduced latency to fall asleep upon SI termination. Electrographic measures in the recovery sleep period following either 6 or 24 h of SI also indicated an elevation of homeostatic sleep drive; specifically, the average NREM episode duration increased (e.g., for 24 h SI, from 2 min, 5 s baseline to 3 min, 19 s following SI), as did the NREM delta power during recovery sleep. Basal forebrain (BF) levels of extracellular adenosine (AD) were also measured with microdialysis sample collection and HPLC detection, as previous work suggests that increasing concentrations of BF AD are related to sleepiness. BF AD levels were significantly elevated during SI, peaking at 220% of baseline during 30 h of SI exposure. These combined findings imply an elevation of the homeostatic sleep drive following either 6 or 24 h of SI, and BF AD levels appear to correlate more with sleepiness than with the cumulative amount of prior wakefulness, since total NREM sleep time declined only slightly. SI may be partially responsible for the symptom of daytime sleepiness observed in a number of clinical disorders, and this may be mediated by mechanisms involving BF AD. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2007 December 27. Published in final edited form as:Neuroscience. Obstructive sleep apnea (OSA) affects 2-4% of the general population (Young et al., 1993), and is characterized by apneic moments during sleep, which are terminated by brief arousals and a reestablishment of the upper airway patency. Thus, sleep fragmentation is a primary physiological disturbance, and may be responsible for some of the symptoms/signs associated with OSA, including excessive daytime sleepiness, which is a principal presenting complaint of patients (Roth et a...

show abstract

Adenosine and Sleep Homeostasis in the Basal Forebrain

Cited by 186 publications

References 59 publications

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

Identification of a population of sleep-active cerebral cortex neurons

Sleep fragmentation elevates behavioral, electrographic and neurochemical measures of sleepiness

Contact Info

Product

Resources

About