Sleep Related Changes in Blood Pressure in Hypocretin-Deficient Narcoleptic Mice

Bastianini, Stefano; Silvani, Alessandro; Berteotti, Chiara; Jl, Elghozi; Franzini, Carlo; Lenzi, P; Martire, Viviana Carmen Lo; Zoccoli, Giovanna

doi:10.1093/sleep/34.2.213

Cited by 71 publications

(109 citation statements)

References 40 publications

(59 reference statements)

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“…2A also indicates that ABP and HR increased upon awakening significantly less in ORX-ATX3 mice, which lack the orexin neurons, than in wild-type mice. 36 This observation fits with previous evidence 38 that ABP was higher during sleep, but not during wakefulness, in either young adult ORX-ATX3 mice lacking orexin neurons 37 or young adult orexin knockout (ORX-KO) mice lacking orexin peptides 40 than in wild-type mice. There is substantial evidence that orexin neurons co-release dynorphin and glutamate, and more contrasting evidence that at least some of these neurons co-express nociceptin/orphanin FQ, galanin, neurotensin, and GABA (cf.…”

Section: Changes In Abp and Hr Upon Awakening From Nrem Sleepsupporting

confidence: 90%

“…However, the finding of similar ABP derangements in ORX-ATX3 mice and ORX-KO mice with respect to wild-type mice suggests that the lack of orexin release, as opposed to the lack of other transmitters co-released by orexin neurons, is sufficient to alter ABP during sleep. 38 These data, 38 as well as those reported in Fig. 2A, 36 were obtained on mice with a "pure" C57Bl6/J genetic background.…”

Section: Changes In Abp and Hr Upon Awakening From Nrem Sleepsupporting

confidence: 57%

“…37 As a result, these mice undergo a progressive loss of orexin neurons, which becomes virtually complete in young adulthood. 37,38 These mice may therefore be considered a model of NT1 with good construct validity.…”

Section: Changes In Abp and Hr Upon Awakening From Nrem Sleepmentioning

confidence: 99%

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Orexins and the cardiovascular events of awakening

Silvani

2017

Temperature

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This brief review aims to provide an updated account of the cardiovascular events of awakening, proposing a testable conceptual framework that links these events with the neural control of sleep and the autonomic nervous system, with focus on the hypothalamic orexin (hypocretin) neurons. Awakening from non-rapid-eye-movement sleep entails coordinated changes in brain and cardiovascular activity: the neural "flip-flop" switch that governs state transitions becomes biased toward the ascending arousal systems, arterial blood pressure and heart rate rise toward waking values, and distal skin temperature falls. Arterial blood pressure and skin temperature are sensed by baroreceptors and thermoreceptors and may positively feedback on the brain wake-sleep switch, thus contributing to sharpen, coordinate, and stabilize awakening. These effects may be enhanced by the hypothalamic orexin neurons, which may modulate the changes in blood pressure, heart rate, and skin temperature upon awakening, while biasing the wake-sleep switch toward wakefulness through direct neural projections. A deeper understanding of the cardiovascular events of awakening and of their links with skin temperature and the wake-sleep neural switch may lead to better treatments options for patients with narcolepsy type 1, who lack the orexin neurons.

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Section: Changes In Abp and Hr Upon Awakening From Nrem Sleepsupporting

confidence: 90%

Section: Changes In Abp and Hr Upon Awakening From Nrem Sleepsupporting

confidence: 57%

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Orexins and the cardiovascular events of awakening

Silvani

2017

Temperature

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“…Our findings are similar to those reported previously in rats (Ootsuka et al, 2009, Blessing et al, 2012. Thus, the present data is consistent with the view that the ultradian alternation of rest-active states is a fundamental part of animal life (Aschoff and Gerkema, 1985, Ootsuka et al, 2011, Blessing et al, 2012, 2013.Previous studies, using EEG-based wake-sleep scoring, show robust changes in behavioural and physiological parameters upon waking (Mochizuki et al, 2006, Zhang et al, 2007, Bastianini et al, 2011, Lo Martire et al, 2012, Silvani et al, 2014, Bastianini et al, 2015. Zhang and colleagues performed simultaneous recording of different behavioural and physiological parameters in mice, including EEG and food intake, observed that eating occurs approximately 15 min after waking (Zhang et al, 2007).…”

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confidence: 93%

The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning

Kuwaki

Ootsuka

2016

Neuroscience

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Our series of rat experiments have shown that locomotor activity, arousal level, body and brown adipose tissue temperatures, heart rate and arterial pressure increase episodically in an integrated manner approximately every 100 min (ultradian manner).Although it has been proposed that the integrated ultradian pattern is a fundamental biological rhythm across species, there are no reports of the integrated ultradian pattern in species other than rats. The aim of the present study was to establish a mice model using simultaneous recording of locomotor activity, eating behaviour, body temperature, heart rate and arousal in order to determine whether their behaviour and physiology are organised in an ultradian manner in normal (wild type) mice. We also incorporated the same recording in prepro-orexin knockout mice to reveal the role of orexin in the brain mechanisms underlying ultradian patterning. The orexin system is one of the key conductors required for coordinating autonomic functions and behaviours, and thus may contribute to ultradian patterning. In wild type mice, locomotor activity, arousal level, body temperature and heart rate increased episodically every 93±18 min (n=8) during 24 hours. Eating was integrated into the ultradian pattern, commencing 23±4 min (n=8) after the onset of an EEG ultradian episode. The integrated ultradian pattern in wild type mice is very similar to that observed in rats. In prepro-orexin knockout mice, the ultradian episodic changes in locomotor activity, EEG arousal indices and body temperature were significantly attenuated, but the ultradian patterning was preserved. Our findings support the view that the ultradian pattern is common across species. The present results also suggest that orexin contributes to driving ultradian episodic changes, however, this neuropeptide is not essential for the generation of the ultradian pattern. Keywordsultradian, orexin knockout mice, body temperature, arousal level, hypothalamus 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 IntroductionCircadian variation in behavioural and physiological parameters is well established.What is not so well recognized is the integrated fashion in which each parameter varies within each phase of the day/night cycle as the animal alternates between inactive and active states (Richter, 1927, Honma and Hiroshige, 1978, Shimada and Marsh, 1979, Livnat et al., 1984, Stupfel et al., 1985, Alfoldi et al., 1990, Holstein-Rathlou et al., 1995. It is proposed that, in addition to circadian patterning, ultradian (<24 hour) alternation between active interaction with the external environment and rest is a fundamental part of animal life (Aschoff and Gerkema, 1985, Ootsuka et al., 2011, Blessing et al., 2012, 2013, Blessing and Ootsuka, 2016. The ultradian pattern, also referred to as the basic-rest activity ...

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“…The effects of genetic manipulation on cardiovascular function have been studied in both orexin peptide knockout mice and orexin neuron-ablated orexin/ataxin-3 transgenic mice and rats, leading to a conflicting data set regarding the effects on heart rate and blood pressure (Kayaba et al, 2003;Schwimmer et al, 2006;Zhang et al, 2006;Schwimmer et al, 2010;Bastianini et al, 2011). The relevance of either of these genetic models to the pharmacological antagonism of orexin receptors in humans is unknown.…”

Section: B Orexin Influences On Peripheral Physiologymentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

et al. 2012

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Sleep Related Changes in Blood Pressure in Hypocretin-Deficient Narcoleptic Mice

Abstract: Chronic lack of hypocretin signaling may entail consequences on blood pressure that are potentially adverse and that vary widely among wake-sleep states.

Cited by 71 publications

References 40 publications

Orexins and the cardiovascular events of awakening

Orexins and the cardiovascular events of awakening

The integrated ultradian organization of behavior and physiology in mice and the contribution of orexin to the ultradian patterning

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

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