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Neuroscience (Impact Factor: 3.36). 07/2007; 146(4):1462-73. DOI: 10.1016/j.neuroscience.2007.03.009
Source: PubMed


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 24 h of SI resembled sleep of the apneic patient in the following ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM) sleep time was greatly reduced, non-rapid eye movement (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 24 h 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 high performance liquid chromatography 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.

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Available from: Mahesh M Thakkar, Jan 10, 2014
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    • "Chronic sleep restriction had been shown to have a negative impact on spatial learning and memory in some studies (McCoy et al., 2013). Other recent studies have focused on deleterious effects on learning and memory due to sleep interruption or SF, which is seen in sleep disorders such as sleep apnea(Tartar et al., 2006; Ward et al., 2009a; Ward et al., 2009b; McKenna et al., 2007). "
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    ABSTRACT: To examine the differential effects of acute and chronic sleep fragmentation (SF) on spatial learning and memory, and hippocampal long-term potentiation (LTP) in pubertal mice. Two studies were performed during which adolescent C57/Bl6 mice were subjected to acute-SF 24h a day x 3 days or chronic-SF for 12h a day x 2 weeks using a programmable rotating lever that provides tactile stimulus with controls housed in similar cages. Spatial learning and memory was examined using the Morris water maze, and long-term potentiation (LTP) was evaluated after stimulation of Schaffer collaterals in CA1 hippocampus post SF. Actigraphy was used during the period of SF to monitor rest-activity patterns. Electroencephalographic (EEG) recordings were acquired for analysis of vigilance state patterns and delta-power. Serum corticosterone was measured to assess stress levels. Acute-SF via tactile stimulation negatively impacted spatial learning, as well as LTP maintenance, compared to controls with no tactile stimulation. While actigraphy showed significantly increased motor activity during SF in both groups, EEG data indicated that overall sleep efficiency did not differ between baseline and SF days, but significant increases in number of wakeful bouts and decreases in average NREM and REM bout lengths were seen during lights-on. Acute sleep fragmentation did not impact corticosterone levels. The current results indicate that, during development in pubertal mice, acute-SF for 24h a day x 3 days negatively impacted spatial learning and synaptic plasticity. Further studies are needed to determine if any inherent long-term homeostatic mechanisms in the adolescent brain afford greater resistance to the deleterious effects of chronic-SF. Copyright © 2015 Elsevier B.V. All rights reserved.
    Brain research 05/2015; 1615. DOI:10.1016/j.brainres.2015.04.037 · 2.84 Impact Factor
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    • "K.M. Ringgold et al. / Journal of Neuroscience Methods 219 (2013) 104– 112 111 they engage in general cage activity, such as grooming, eating and drinking. Therefore, it is not necessary to include an additional control manipulation to account for locomotor activity, such as necessary when a treadmill or a continuously rotating disc or drum is used to deprive an animal of total sleep (Barf et al., 2010; Leenaars et al., 2011; McKenna et al., 2007). In addition to the software features that control the disc rotation schedule, the motor and drive system are extremely quiet, and the stepper motor provides a very smooth disc rotation. "
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    ABSTRACT: Sleep disruption is a frequent occurrence in modern society. Whereas many studies have focused on the consequences of total sleep deprivation, few have investigated the condition of sleep disruption. We disrupted sleep of mice during the light period for 9 consecutive days using an intermittently-rotating disc. Electroencephalogram (EEG) data demonstrated that non-rapid eye movement (NREM) sleep was severely fragmented and REM sleep was essentially abolished during the 12h light period. During the dark period, when sleep was not disrupted, neither NREM sleep nor REM sleep times differed from control values. Analysis of the EEG revealed a trend for increased power in the peak frequency of the NREM EEG spectra during the dark period. The fragmentation protocol was not overly stressful as body weights and water consumption remained unchanged, and plasma corticosterone did not differ between mice subjected to 3 or 9 days of sleep disruption and home cage controls. However, mice subjected to 9 days of sleep disruption by this method responded to lipopolysaccharide with an exacerbated febrile response. Existing methods to disrupt sleep of laboratory rodents often subject the animal to excessive locomotion, vibration, or sudden movements. This method does not suffer from any of these confounds. This study demonstrates that prolonged sleep disruption of mice exacerbates febrile responses to lipopolysaccharide. This device provides a method to determine mechanisms by which chronic insufficient sleep contributes to the etiology of many pathologies, particularly those with an inflammatory component.
    Journal of Neuroscience Methods 07/2013; 219(1). DOI:10.1016/j.jneumeth.2013.07.008 · 2.05 Impact Factor
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    • "However, microdialysis probes are estimated to recover only 10–20% of the adenosine [66], suggesting estimates in the low hundreds nanomolar range. As adenosine release is activity dependent and given the increased metabolic rate of the brain during wakefulness [68], [69], elevation of adenosine concentrations have been observed to follow a diurnal rhythm, increasing during the wake phase and declining during sleep [9], [70]. Sleep deprivation for 6 h in cats induced a 40% increase in BFB adenosine levels [7], [8]. "
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    ABSTRACT: Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K(+), AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.
    PLoS ONE 01/2013; 8(1):e53814. DOI:10.1371/journal.pone.0053814 · 3.23 Impact Factor
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