Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep

Feng, Hui; Wen, Si‐Yi; Qiao, Qi‐Cheng; Pang, Yu-Jie; Wang, Shengyun; Li, Hao-Yi; Cai, Jiao; Zhang, Kaixuan; Chen, Jing; Hu, Zhian; Luo, Fenlan; Wang, Guanzhong; Yang, Ning; Zhang, Jun

doi:10.1038/s41467-020-17401-3

Cited by 53 publications

(50 citation statements)

References 68 publications

(125 reference statements)

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“…Alternatively, children with migraine may be biologically sleepier than their healthy counterparts. This is at odds with findings from actigraphy 42 and questionnaire-based studies 43 in pediatric migraine patients which found longer SOL in patients compared to healthy controls. Although, actigraphy and self-report data are less accurate than PSG, particularly for SOL 44 .…”

Section: Polysomnography -Childrenmentioning

confidence: 78%

“… 39 Furthermore, cutaneous allodynia, a prominent symptom during migraine attacks, has been shown to worsen in response to REM sleep deprivation, 3 thus indicating potential dysfunction in mechanisms underlying REM-NREM or REM-wake transitions in migraine. A plausible neural correlate for this is the hypothalamic orexinergic system, which plays a critical role in stabilizing sleep/wake transitions and REM sleep, 40 and is linked to migraine, suggesting multiple points of intersection between sleep and trigeminal pain. This is speculative, and the relationship with REM sleep is likely to be complex.…”

Section: Discussionmentioning

confidence: 99%

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Subjective Sleep Quality and Sleep Architecture in Patients With Migraine

et al. 2021

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Objectives:Sleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraine patients. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI), and objective sleep architecture measured using polysomnography between adult and pediatric patients, and healthy controls.Methods:This review was pre-registered on PROSPERO (CRD42020209325). A systematic search of five databases (Embase, MEDLINE®, Global Health, APA PsycINFO, APA PsycArticles, last searched: 12/17/2020) was conducted to find case-controlled studies which measured polysomnography and/or PSQI in patients with migraine. Pregnant participants and those with other headache disorders were excluded. Effect sizes (Hedges’ g) were entered into a random effects model meta-analysis. Study quality was evaluated with the Newcastle Ottawa Scale, and publication bias with Egger’s regression test.Results:32 studies were eligible, of which 21 measured PSQI and/MIDAS in adults, 6 measured PSG in adults and 5 in children. The overall mean study quality score was 5/9, and this did not moderate any of the results, and there was no risk of publication bias. Overall, adults with migraine had higher PSQI scores than healthy controls (g=0.75, p < .001, 95% confidence interval [95%CI]: 0.54 - 0.96). This effect was larger in those with chronic rather than episodic condition (g=1.03, p < .001, 95%CI: 0.37 - 1.01, g = 0.63, p < .001, 95%CI: 0.38 - 0.88 respectively). For polysomnographic studies, adults and children with migraine displayed a lower percentage of REM sleep (g=-0.22, p = 0.017, 95%CI: -0.41 - -0.04, g = -0.71, p = 0.025, 95%CI: -1.34 - -0.10 respectively) than controls. Pediatric patients displayed less total sleep time (g=-1.37, p = 0.039, 95%CI: -2.66 - -0.10), more wake (g=0.52, p < .001, 95%CI: 0.08 – 0.79) and shorter sleep onset latency (g=-0.37, p < .001, 95%CI: -0.54 - -0.21) than controls.Discussion:People with migraine have significantly poorer subjective sleep quality and altered sleep architecture compared to healthy individuals. Further longitudinal empirical studies are required to enhance our understanding of this relationship.

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Section: Polysomnography -Childrenmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Subjective Sleep Quality and Sleep Architecture in Patients With Migraine

et al. 2021

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“…Interestingly, sleep impairments such as insomnia, fragmented sleep and narcolepsy are common in PD patients [ 83 ]. The orexins play a major role in the regulation of sleep [ 84 ] and thus it is not surprising that orexin system dysregulation results in various sleep impairments, including destabilization and loss of REM sleep [ 34 , 85 , 86 ], more sleep to wake transitions [ 26 ], and sleep fragmentation [ 87 ]. Perhaps the most interesting link between the orexin system and PD is narcolepsy, which is commonly experienced by PD patients [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease

Stanojlović

Pallais

Kotz

2021

IJMS

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Aside from the classical motor symptoms, Parkinson’s disease also has various non-classical symptoms. Interestingly, orexin neurons, involved in the regulation of exploratory locomotion, spontaneous physical activity, and energy expenditure, are affected in Parkinson’s. In this study, we hypothesized that Parkinson’s-disease-associated pathology affects orexin neurons and therefore impairs functions they regulate. To test this, we used a transgenic animal model of Parkinson’s, the A53T mouse. We measured body composition, exploratory locomotion, spontaneous physical activity, and energy expenditure. Further, we assessed alpha-synuclein accumulation, inflammation, and astrogliosis. Finally, we hypothesized that chemogenetic inhibition of orexin neurons would ameliorate observed impairments in the A53T mice. We showed that aging in A53T mice was accompanied by reductions in fat mass and increases in exploratory locomotion, spontaneous physical activity, and energy expenditure. We detected the presence of alpha-synuclein accumulations in orexin neurons, increased astrogliosis, and microglial activation. Moreover, loss of inhibitory pre-synaptic terminals and a reduced number of orexin cells were observed in A53T mice. As hypothesized, this chemogenetic intervention mitigated the behavioral disturbances induced by Parkinson’s disease pathology. This study implicates the involvement of orexin in early Parkinson’s-disease-associated impairment of hypothalamic-regulated physiological functions and highlights the importance of orexin neurons in Parkinson’s disease symptomology.

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“…This indicates a potential dysfunction in mechanisms underlying REM-NREM or REM-wake transitions in migraineurs. A plausible neural correlate for this is the hypothalamic orexinergic system which plays a critical role in stabilizing sleep/wake transitions and REM sleep 34 , and has been linked to migraine, suggesting multiple points of intersection between sleep and trigeminal pain. Although, this is speculative, and the relationship with REM sleep is likely to be complex and bi-directional.…”

Section: Discussionmentioning

confidence: 99%

Subjective sleep quality and objective sleep physiology in migraineurs: a meta-analysis

Stanyer

Creeney

Nesbitt

et al. 2021

Preprint

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Objectives: Sleep disturbance is often associated with migraine. However, there is a paucity of research investigating objective and subjective measures of sleep in migraineurs. This meta-analysis aims to determine whether there are differences in subjective sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) and objective sleep physiology measured using polysomnography between adult and pediatric migraineurs, and healthy controls. Methods: A systematic search of five databases was conducted to find case-controlled studies which measured polysomnography and/or PSQI in migraineurs. Effect sizes (Hedges' g) were entered into a random effects model meta-analysis. Results: 32 separate studies were eligible. Overall, adult migraineurs had higher PSQI scores than healthy controls (g = 0.75, p < .001). This effect was larger in chronic than episodic migraineurs (g = 1.03, p < .001, g = 0.63, p < .001 respectively). For polysomnographic studies, adult and pediatric migraineurs displayed a lower percentage of REM sleep (g = -0.22, p = 0.017, g = -0.71, p = 0.025 respectively) than healthy controls. Pediatric migraineurs also displayed less total sleep time (g = -1.37, p = 0.039), more wake (g = 0.52, p < .001) and shorter sleep onset latency (g = -0.37, p < .001) than healthy controls. Conclusion: Migraineurs have significantly poorer subjective sleep quality, and altered sleep compared to healthy individuals - a finding which is particularly evident in children. This has implications for developing appropriate treatments. Further longitudinal empirical studies are required to enhance our understanding of this relationship.

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Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep

Cited by 53 publications

References 68 publications

Subjective Sleep Quality and Sleep Architecture in Patients With Migraine

Subjective Sleep Quality and Sleep Architecture in Patients With Migraine

Inhibition of Orexin/Hypocretin Neurons Ameliorates Elevated Physical Activity and Energy Expenditure in the A53T Mouse Model of Parkinson’s Disease

Subjective sleep quality and objective sleep physiology in migraineurs: a meta-analysis

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