1,721,231 research outputs found
Agonisti orexinergici innovativi per la terapia della narcolessia
No full textLa narcolessia di tipo 1 (NT1) è una patologia invalidante causata dalla morte dei neuroni che rilasciano due neuropeptidi, le orexine. La terapia sostituiva della NT1 con le orexine sarebbe dunque quella ottimale su base eziologica. Purtroppo, l’efficacia terapeutica delle orexine somministrate per via sistemica è limitata dal loro insufficiente trasporto attraverso la barriera emato-encefalica (BEE).
Questo progetto mira a porre le basi per una terapia innovativa della NT1 su base eziologica:
1) sintetizzando un peptide artificiale con struttura innovativa, dotato di attività agonista orexinergica e capace di attraversare la BEE;
2) verificando in vitro che questo peptide evochi risposte intracellulari attraverso il legame a recettori per le orexine;
3) verificando in un modello murino di NT1 che questo peptide, somministrato per via sistemica, attraversi la BEE attenuando le alterazioni del ciclo veglia-sonno e la cataplessia, che sono i segni caratteristici della NT1
Frontiers in Neuroscience
No full textFrontiers in Neuroscience, section on Sleep and Circadian Rhythms
All animals sleep. Yet, the underlying principles of why we sleep are still unknown. What constitute arousal states? Defining arousal and brain states in neurobiological terms is significant, as changes in arousal are at the core of most neuropsychiatric disorders. The new section of Frontiers aims to increase our understanding of the neuronal underpinnings of sleep and circadian rhythms, two converging biological processes essential for neuronal stability
Sleep disorders, nocturnal blood pressure, and cardiovascular risk: A translational perspective
No full textCardiovascular disease (CVD) represents the first cause of death globally. The nighttime is generally a period of relative protection from CVD events such as myocardial infarction, sudden cardiac death, and stroke, at least compared to the early morning period. The nighttime also generally entails lower values of arterial blood pressure (ABP) and heart rate (HR) and higher cardiac parasympathetic modulation. These day-night cardiovascular rhythms are ultimately driven by circadian molecular oscillators in the hypothalamic suprachiasmatic nucleus and in peripheral cells, including those in the heart, blood vessels, and kidneys. The wake-sleep states are intermediate mechanisms of circadian cardiovascular regulation, with non-REM sleep decreasing ABP and HR and increasing cardiac parasympathetic modulation at the beginning of the night. Obstructive sleep apnea, insomnia, and the restless legs syndrome have high prevalence in the general population and may increase nighttime cardiovascular activity and CVD risk. CVD risk is better predicted by ABP values during nighttime sleep than during daytime wakefulness. Higher nighttime values of ABP and HR increase cardiac work and vessel wall stress. During the night, circadian rhythms may enhance cardiac responses to hypertrophic stimuli, increase vascular smooth muscle Rho kinase activity and contractility, decrease endothelial nitric oxide production and vascular responses to vasodilators, and increase circulating monocytes with the potential to infiltrate atherosclerotic plaques. Together, these factors configure a “perfect storm” scenario that may make increased cardiovascular activity during the night a final common mechanism linking sleep disorders to CVD risk
Autonomic nervous system dysfunction in narcolepsy type 1: time to move forward to the next level?
No full textThis editorial has no asbtrac
Plos One
No full textThe world’s first multidisciplinary Open Access journal, PLOS ONE accepts scientifically rigorous research, regardless of novelty. PLOS ONE’s broad scope provides a platform to publish primary research, including interdisciplinary and replication studies as well as negative results. The journal’s publication criteria are based on high ethical standards and the rigor of the methodology and conclusions reported
Orexins and the cardiovascular events of awakening
No full textThis 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
The link between narcolepsy and autonomic cardiovascular dysfunction: a translational perspective.
No full textNarcolepsy is a rare disease that entails excessive daytime sleepiness, often associated with sudden episodes of muscle weakness known as cataplexy. Narcolepsy with cataplexy (NC) is due to the loss of hypothalamic neurons that release the neuropeptides orexin A and B. Orexin neuron projections prominently target brain structures involved in wake-sleep state switching and the central autonomic network. This review provides an updated summary of the links between NC and autonomic cardiovascular dysfunction from a translational perspective. The available evidence suggests that, compared with control subjects, the heart rate in patients and animal models with NC is variable during wakefulness and normal to high during sleep. Responses of the heart rate to internal stimuli (arousal from sleep, leg movements during sleep, defense response) are blunted. These alterations result from orexin deficiency and, at least during wakefulness before sleep, involve decreased parasympathetic modulation of the heart rate. On the other hand, NC in patients and animal models is associated with a blunted fall in arterial blood pressure from wakefulness to sleep, and particularly to the REM state, coupled to a variable decrease in arterial blood pressure during wakefulness. The former effect is caused, at least in part, by deranged control of the heart, whereas the latter may be due to decreased vasoconstrictor sympathetic activity. Systematic studies are warranted to help clarify whether and how the links between NC and autonomic dysfunction impact on the cardiovascular risk of patients with narcolepsy
Night, darkness, sleep, and cardiovascular activity.
No full textWe humans tend to spend a significant fraction of the night asleep in the dark and to stay awake with daylight. However, the widespread availability of electrical power is progressively imparting 24/7 activity schedules to our modern societies, in which artificial ambient light and illuminated screens of electronic devices allow people to stay awake at night for work or leisure, postponing sleep. Sleep disorders such as insomnia and sleep-disordered breathing may reduce the quantity and quality of nocturnal sleep and entail excessive daytime sleepiness as a consequence. Not only these environmental and behavioral factors but also a range of genetic, epigenetic, and age-dependent factors may cause the body to be regulated out of phase with the environment, mimicking in many respect conditions of jet lag associated with long-range flights. This chapter will discuss the effects of night/day, darkness/light, and sleep/wakefulness on cardiovascular activity considering firstly each factor on its own and secondly the interactions among the different factors. The chapter will focus on the control of arterial blood pressure and heart rate in human subjects. The chapter will also touch upon the hemodynamic consequences of the control of vascular resistance and blood volume, as well as upon the bidirectional translation between research on human subjects and model organisms such as mice, which are arguably the mammals of choice for mechanistic studies of functional genomic
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