Sleep phenotype in the Townes mouse model of sickle cell disease

O’Donnell, Brett J.; Guo, Lanping; Ghosh, Samit; Shah, Faraaz; Strollo, Patrick J.; McVerry, Bryan J.; Gladwin, Mark T.; Ofori-Acquah, Solomon Fiifi; Kato, Gregory J.; O’Donnell, Christopher P.

doi:10.1007/s11325-018-1711-x

Cited by 11 publications

(8 citation statements)

References 24 publications

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“…Mice were tethered to a preamplifier system via a custom cable (363-SL/6 80CM 6TCS, Plastics One Inc.) for sleep recordings. Our sleep-wake detection system has previously been described and validated in mice (Benington et al 1994;O'Donnell et al 2019). Sleep-wake states were determined using the frequency distribution of EEG and the amplitude of EMG.…”

Section: Sleep Polysomnography Recordingmentioning

confidence: 99%

“…Continuous EEG and EMG data was recorded as waveforms using WinDaq Data Acquisition Software (v.2.94, DATAQ Instruments, Inc.) and converted into an analyzable format (Stanford Sleep Structure Scoring System) via a custom program (Benington et al 1994), subsequently validated in mice (Veasey et al 2004). Manual sleep-wake state validation was based on previously described parameters (O'Donnell et al 2019). Time spent in NREMS, REMS, and awake states were calculated as the percent of total spent in that state during a complete 24hour period.…”

Section: Sleep-wake State Scoringmentioning

confidence: 99%

“…Fentanyl is a highly potent synthetic opioid used to alleviate pain in certain clinical contexts including during and after surgery and in the treatment of cancer and chronic pain (Comer and Cahill 2019). Fentanyl along with other synthetic opioids have surpassed heroin and oxycodone as the main drivers of overdose deaths and increased rates of opioid use disorder (OUD) in regions with already high base rates of opioid use (Gladden 2016;O'Donnell 2017). Thus, understanding the unique consequences of fentanyl use on health is imperative to developing strategies for treatments to curb the impact.…”

Section: Introductionmentioning

confidence: 99%

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A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

et al. 2022

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Rationale: Synthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal.Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations. Objectives:To determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.Methods: Electroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.Results: Acute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.Conclusions: Chronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

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Section: Sleep Polysomnography Recordingmentioning

confidence: 99%

Section: Sleep-wake State Scoringmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

et al. 2022

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“…Continuous EEG and EMG data was recorded as waveforms using WinDaq Data Acquisition Software (v.2.94, DATAQ Instruments, Inc.) and converted into an analyzable format (Stanford Sleep Structure Scoring System) via a custom program (Benington et al 1994), subsequently validated in mice (Veasey et al 2004). Manual sleep-wake state validation was based on previously described parameters (O’Donnell et al 2019). Time spent in NREMS, REMS, and awake states were calculated as the percent of total spent in that state during a complete 24- hour period.…”

Section: Methodsmentioning

confidence: 99%

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

Gamble

Chuan

Gallego-Martín

et al. 2022

Preprint

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RationaleSynthetic opioids like fentanyl are contributing to the rise in rates of opioid use disorder and drug overdose deaths. Sleep dysfunction and circadian rhythm disruption may worsen during opioid withdrawal and persist during abstinence. Severe and persistent sleep and circadian alterations are putative factors in opioid craving and relapse. However, very little is known about the impact of fentanyl on sleep architecture and sleep-wake cycles, particularly opioid withdrawal. Further, circadian rhythms regulate sleep-wake cycles, and the circadian transcription factor, neuronal PAS domain 2 (NPAS2) is involved in the modulation of sleep architecture and drug reward. Here, we investigate the role of NPAS2 in fentanyl-induced sleep alterations.ObjectivesTo determine the effect of fentanyl administration and withdrawal on sleep architecture, and the role of NPAS2 as a factor in fentanyl-induced sleep changes.MethodsElectroencephalography (EEG) and electromyography (EMG) was used to measure non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) at baseline and following acute and chronic fentanyl administration in wild-type and NPAS2-deficient male mice.ResultsAcute and chronic administration of fentanyl led to increased wake and arousal in both wild-type and NPAS2-deficient mice, an effect that was more pronounced in NPAS2-deficient mice. Chronic fentanyl administration led to decreased NREMS, which persisted during withdrawal, progressively decreasing from day 1 to 4 of withdrawal. The impact of fentanyl on NREMS and arousal was more pronounced in NPAS2-deficient mice.ConclusionsChronic fentanyl disrupts NREMS, leading to a progressive loss of NREMS during subsequent days of withdrawal. Loss of NPAS2 exacerbates the impact of fentanyl on sleep and wake, revealing a potential role for the circadian transcription factor in opioid-induced sleep changes.

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“…C57BL/6J (stock # 000664) mice were obtained from The Jackson Laboratory (Bar Harbor, ME). Cyb5r3 fl/fl Myh11-CreER T2 mice (described in detail in supplemental Materials) 22,29,34 and Townes knockin humanized sickle Hb (SS) mice and their humanized Hb controls (AA and AS) were bred on C57BL/6 and 129S backgrounds 35 and maintained at the University of Pittsburgh. For the Cyb5r3 fl/fl Myh11-CreER T2 mice, the Myh11-driven Cre-ERT transgene resides on the Y chromosome, 36 thus necessitating the use of male mice for all experiments, which were approved by the University of Pittsburgh Institutional Animal Care and Use Committee.…”

Section: Animalsmentioning

confidence: 99%

Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice

Wood¹,

Durgin²,

Schmidt³

et al. 2019

Blood Advances

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Sleep phenotype in the Townes mouse model of sickle cell disease

Abstract: The presence of decreased total NREM sleep associated with reduced arousals, in the absence of OSAS, suggests a distinctive underlying sleep phenotype in a mouse model of SCD.

Cited by 11 publications

References 24 publications

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

A role for the circadian transcription factor NPAS2 in the progressive loss of non-rapid eye movement sleep and increased arousal during fentanyl withdrawal in male mice

Smooth muscle cytochrome b5 reductase 3 deficiency accelerates pulmonary hypertension development in sickle cell mice

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