Ventricular orexin-A (hypocretin-1) levels correlate with rapid-eye-movement sleep without atonia in Parkinson's disease (original) (raw)
Related papers
Hypocretin (orexin) loss in Parkinson's disease
Brain, 2007
The hypothalamic hypocretin (orexin) system plays a central role in the regulation of various functions, including sleep/wake regulation and metabolism. There is a growing interest in hypocretin function in Parkinson's disease (PD), given the high prevalence of non-motor symptoms such as sleep disturbances in this disorder. However, studies measuring CSF hypocretin levels have yielded contradictory results. In PD patients and matched controls, we (i) estimated the number of hypocretin neurons in post-mortem hypothalami using immunocytochemistry and an image analysis system (ii) quantified hypocretin levels in post-mortem ventricular CSF and (iii) prefrontal cortex using a radioimmunoassay. Furthermore, presence of Lewy bodies was verified in the hypothalamic hypocretin cell area. Data are presented as median (25th-75th percentile). We showed a significant decrease between PD patients and controls in (i) the number of hypocretin neurons (PD: 20 276 (13 821-31 229); controls: 36 842 (32 546-50 938); P = 0.016); (ii) the hypocretin-1 concentration in post-mortem ventricular CSF (PD: 365.5 pg/ml (328.0-448.3); controls: 483.5 (433.5-512.3); P = 0.012) and (iii) the hypocretin-1 concentrations in prefrontal cortex (PD: 389.6 pg/g (249.2-652.2); controls: 676.6 (467.5-883.9); P = 0.043). Hypocretin neurotransmission is affected in PD. The hypocretin-1 concentration in the prefrontal cortex was almost 40% lower in PD patients, while ventricular CSF levels were almost 25% reduced. The total number of hypocretin neurons was almost half compared to controls.
European Journal of Neuroscience, 2020
Neuropeptides orexin A and B (OX-A/B, also called hypocretin 1 and 2) are released selectively by a population of neurons which projects widely into the entire central nervous system but are localized in a restricted area of the tuberal region of the hypothalamus, caudal to the paraventricular nucleus. The OX system prominently targets brain structures involved in the Accepted Article This article is protected by copyright. All rights reserved regulation of wake-sleep state switching, and also orchestrates multiple physiological functions. The degeneration and dysregulation of the OX system promotes narcoleptic phenotypes both in humans and animals. Hence, this review begins with the already proven involvement of OX in narcolepsy, but it mainly discusses the new pre-clinical and clinical insights of the role of OX in three major neurological disorders characterized by sleep impairment which have been recently associated with OX dysfunction, such as Alzheimer's disease, stroke and Prader Willi syndrome, and have been emerged over the past 10 years to be strongly associated with the OX dysfunction and should be more considered in the future. In the light of the impairment of the OX system in these neurological disorders, it is conceivable to speculate that the integrity of the OX system is necessary for a healthy functioning body.
Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinson's disease dementia
Brain, 2009
Excessive daytime sleepiness is common in Parkinson's disease and has been associated with Parkinson's disease-related dementia. Narcoleptic features have been observed in Parkinson's disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinson's disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have been inconclusive. Reports of sleep studies in Parkinson's disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinson's disease patients without dementia and 20 Parkinson's disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinson's disease patients without dementia and seven Parkinson's disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinson's disease patients without dementia and Parkinson's disease patients with dementia than controls (P50.01) and scores 410 were more frequent in Parkinson's disease patients with dementia than in Parkinson's disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 AE 47.15 pg/ml; without dementia = 300.99 AE 58.68 pg/ml; with dementia = 309.94 AE 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinson's disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia, but lumbar cerebrospinal http://brain.oxfordjournals.org/ Downloaded from fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinson's disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.
A Brief History of Hypocretin/Orexin and Narcolepsy
Neuropsychopharmacology, 2001
The hypothalamic peptides named the orexins, or hypocretins, were discovered in 1998. In 1999 it was established that genetic narcolepsy could be caused by mutations in the genes synthesizing these peptides or their receptors. In September of 2000 it was found that most human narcolepsy is caused by loss of hypocretin cells, most likely as a result of a degenerative process. This paper reviews these events and their implications for our understanding of brain arousal and motor control systems.
Bioscientia Medicina : Journal of Biomedicine and Translational Research, 2021
Introduction: There are many areas of brain degeneration in people with Parkinson's disease. The dopaminergic degeneration process in the midbrain causes early symptoms of sleep disturbances. Hypocretin produced by the hypothalamus is involved in the pathophysiology of Parkinson's disease. Some research results regarding the relationship between plasma hypocretin levels and sleep disorders in patients with Parkinson's disease are still controversial. Method: This research is a cross sectional study in Neurology Polyclinic Dr. M. Djamil Padang and Network Hospital. All research subjects measured hypocretin levels and sleep disorders using the Epworth Sleepiness Scale. Statistical analysis was performed on a computerized basis using IBM SPSS statistics version 23.0 for windows. Result: A total of 60 patients with Parkinson's disease were included in this study, 30 subjects experienced sleep disorders and 30 others had no sleep disorders. There was a significant differe...
Hypocretin/orexin disturbances in neurological disorders
Sleep Medicine Reviews, 2009
The hypothalamic hypocretin (orexin) system plays a crucial role in the regulation of sleep and wakefulness. The strongest evidence for this is the fact that the primary sleep disorder narcolepsy is caused by disrupted hypocretin signaling in humans as well as various animal models. There is a growing interest in the role of hypocretin defects not only in the pathophysiology of other sleep disorders, but also in neurological diseases with associated sleep symptomatology. In this paper we first review the current methods to measure the integrity of the hypocretin system in human patients. The most widely used technique entails the measurement of hypocretin-1 in lumbar cerebrospinal fluid. In addition, hypocretin levels can be measured in ventricular cerebrospinal fluid and brain tissue extract. Finally, in post-mortem hypothalamic material, the number of hypocretin neurons can be precisely quantified. In the second part of this paper we describe the various neurological disorders in which hypocretin defects have been reported. These include neurodegenerative, neuromuscular and immune-mediated diseases, as well as traumatic brain injury. We conclude with a discussion of the functional relevance of partial hypocretin defects, and the various pathophysiological mechanisms that can lead to such defects.
Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinson's disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease.