An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep

Perentos, Nicholas; Martins, Amadeu; Cumming, R. J. M.; Mitchell, Nadia L.; Palmer, David N.; Sawiak, Stephen J.; Morton, A. Jennifer

doi:10.1523/jneurosci.4295-15.2016

Cited by 32 publications

(21 citation statements)

References 53 publications

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“…; Borbély, ; Perentos et al . ). In humans, sleep changes profoundly across pregnancy (Facco et al .…”

Section: Discussionmentioning

confidence: 97%

“…Although accelerometers do not directly measure sleep, given that the timing of rest and activity followed the SSW exposure, we can assume that sleep timing has also been disrupted. Sleep in sheep and humans is under homeostatic regulation, with decreasing slow wave activity across a night of sleep and increased sleep pressure following sleep deprivation (Borbély et al 1981;Borbély, 1982;Perentos et al 2016). In humans, sleep changes profoundly across pregnancy (Facco et al 2010) and poor quality or a short duration of sleep are associated with poor maternal metabolic outcomes including increased rates of gestational diabetes, as well as adverse pregnancy outcomes including preterm birth and small for gestational age (Abeysena et al 2009;Facco et al 2017).…”

Section: Palmermentioning

confidence: 99%

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Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

Gatford

Kennaway

Liu

et al. 2019

The Journal of Physiology

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Key points Shift work impairs metabolic health, although its effects during pregnancy are not well understood We evaluated the effects of a simulated shift work protocol for one‐third, two‐thirds or all of pregnancy on maternal and pregnancy outcomes in sheep. Simulated shift work changed the timing of activity, disrupted hormonal and cellular rhythms, and impaired maternal glucose tolerance during early pregnancy. Gestation length was increased in twin pregnancies, whereas singleton lambs were lighter at a given gestational age if mothers were subjected to shift work conditions in the first one‐third of pregnancy. Exposure to rotating night and day shifts, even if only in early pregnancy, may adversely affect maternal metabolic and pregnancy outcomes. Abstract Shift workers are at increased risk of developing type 2 diabetes and obesity; however, the impact during pregnancy on maternal metabolism is unknown. Using a large animal model, we assessed the impact of simulated shift work (SSW) exposure during pregnancy on maternal circadian rhythms, glucose tolerance and pregnancy outcomes. Following mating, ewes were randomly allocated to a control photoperiod (CON 12 h light, 12 h dark) or to SSW, where the timing of light exposure and food presentation was reversed twice each week for one‐third, two‐thirds or all of pregnancy. Maternal behaviour followed SSW cycles with increased activity during light exposure and feeding. Melatonin rhythms resynchronized within 2 days of the photoperiod shift, whereas peripheral circadian rhythms were arrhythmic. SSW impaired glucose tolerance (+29%, P = 0.019) and increased glucose‐stimulated insulin secretion (+32%, P = 0.018) in ewes with a singleton fetus in early but not late gestation. SSW exposure did not alter rates of miscarriage or stillbirth, although it extended gestation length in twin pregnancies (+2.4 days, P = 0.032). Relative to gestational age, birth weight was lower in singleton progeny of SSW than CON ewes (–476 g, P = 0.016). These results have implications for the large number of women currently engaged in shift work, and further studies are required to determine progeny health impacts.

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“…; Borbély, ; Perentos et al . ). In humans, sleep changes profoundly across pregnancy (Facco et al .…”

Section: Discussionmentioning

confidence: 97%

Section: Palmermentioning

confidence: 99%

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

Gatford

Kennaway

Liu

et al. 2019

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…The surgery for implanting electrodes was conducted as described by Perentos et al (2016Perentos et al ( , 2017. Briefly, subdural electrodes (3 mm diameter Â 1 mm deep Ag/AgCl discs; NDimension (Science and Engineering) were implanted at sites across the cortex (Fig.…”

Section: Surgerymentioning

confidence: 99%

“…2A). Seven vigilance stages were separated based on previously published criteria (Perentos et al, 2016). W was defined by low-voltage high-frequency EEG accompanied by increased EMG activity and intensive but irregular ocular movements.…”

Section: Sleep Stagesmentioning

confidence: 99%

“…Their husbandry and welfare is easily managed, particularly when compared with nonhuman primates (Morton and Howland, 2013). Techniques for EEG monitoring in sheep are already well established (Perentos et al, 2016), and telemetric data collection allows continuous longitudinal recording across night and day. We used automated detection methods to identify spindle characteristics in sheep from recordings made continuously over a 34 h period.…”

Section: Introductionmentioning

confidence: 99%

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Characterizing Sleep Spindles in Sheep

Schneider

Vas

Nicol

et al. 2020

eNeuro

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Sleep spindles are distinctive transient patterns of brain activity that typically occur during non-rapid eye movement (NREM) sleep in humans and other mammals. Thought to be important for the consolidation of learning, they may also be useful for indicating the progression of aging and neurodegenerative diseases. The aim of this study was to characterize sleep spindles in sheep (Ovis aries). We recorded electroencephalographs wirelessly from six sheep over a continuous period containing 2 nights and a day. We detected and characterized spindles using an automated algorithm. We found that sheep sleep spindles fell within the classical range seen in humans (10-16 Hz), but we did not see a further separation into fast and slow bands. Spindles were detected predominantly during NREM sleep. Spindle characteristics (frequency, duration, density, topography) varied between individuals, but were similar within individuals between nights. Spindles that occurred during NREM sleep in daytime were indistinguishable from those found during NREM sleep at night. Surprisingly, we also detected numerous spindle-like events during unequivocal periods of wake during the day. These events were mainly local (detected at single sites), and their characteristics differed from spindles detected during sleep. These "wake spindles" are likely to be events that are commonly categorized as "spontaneous alpha activity" during wake. We speculate that wake and sleep spindles are generated via different mechanisms, and that wake spindles play a role in cognitive processes that occur during the daytime.Sleep spindles provide an indication of brain health and function. In this study, we characterize sleep spindles in sheep (Ovis aries) for the first time. We found that sleep spindles in sheep are similar to those found in humans in many respects (e.g., density, duration, and frequency) and occurred mainly during non-rapid eye movement sleep. Interestingly however, we also saw spindles during wake in the day. Spindles detected during wake were characteristically distinct from those occurring during sleep. We suggest that wake and sleep spindles are generated via different mechanisms and may have different functional roles. Wake spindles may be a component of cognitive processes that occur during the daytime, such as memory retrieval and attention.

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Large-Brained Animal Models of Huntington’s Disease: Sheep

Morton

2018

Methods in Molecular Biology

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The limitations of using small-brained rodents to model diseases that affect large-brain humans are becoming increasingly obvious as novel therapies emerge. Huntington's disease (HD) is one such disease. In recent years, the desirability of a large-brained, long-lived animal model of HD for preclinical testing has changed into a necessity. Treatment involving gene therapy in particular presents delivery challenges that are currently unsolved. Models using long-lived, large-brained animals would be useful, not only for refining methods of delivery (particularly for gene and other therapies that do not involve small molecules) but also for measuring long-term "off-target" effects, and assessing the efficacy of therapies. With their large brains and convoluted cortices, sheep are emerging as feasible experimental subjects that can be used to bridge the gap between rodents and humans in preclinical drug development. Sheep are readily available, economical to use, and easy to care for in naturalistic settings. With brains of a similar size to a large rhesus macaque, they have much to offer. The only thing that was missing until recently was the means of testing their neurological function and behavior using approaches and methods that are relevant to HD. In this chapter, I will outline the present and future possibilities of using sheep and testing as large animal models of HD.

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An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep

Abstract: sheep. We conclude that, whereas sleep homeostasis is present in CLN5 Ϫ/Ϫ sheep, underlying CLN5 Ϫ/Ϫ disease processes prevent its full expression, even at early stages. Such deficits may contribute to early abnormalities seen in sheep and patients and warrant further study.

Cited by 32 publications

References 53 publications

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

Characterizing Sleep Spindles in Sheep

Large-Brained Animal Models of Huntington’s Disease: Sheep

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