Major alteration of motor control during rapid eye movements sleep in mice models of sleep disorders.

Alteration of motor control during rapid eye movements (REM) sleep has been extensively described in sleep disorders, in particular in isolated REM sleep behavior disorder (iRBD) and narcolepsy type 1 (NT1). NT1 is caused by the loss of orexin/hypocretin (ORX) neurons. Unlike in iRBD, the RBD comorbid symptoms of NT1 are not associated with alpha-synucleinopathies.

Precocious puberty in narcolepsy type 1: Orexin loss and/or neuroinflammation, which is to blame?

Narcolepsy type 1 (NT1) is a rare neurological sleep disorder triggered by postnatal loss of the orexin/hypocretin neuropeptides. Overweight/obesity and precocious puberty are highly prevalent comorbidities of NT1, with a close temporal correlation with disease onset, suggesting a common origin. However, the underlying mechanisms remain unknown and merit further investigation.

Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy.

Narcolepsy with cataplexy or narcolepsy type 1 is a disabling chronic sleep disorder resulting from the destruction of orexinergic neurons in the hypothalamus. The tight association of narcolepsy with HLA-DQB1*06:02 strongly suggest an autoimmune origin to this disease. Furthermore, converging epidemiological studies have identified an increased incidence for narcolepsy in Europe following Pandemrix® vaccination against the 2009-2010 pandemic 'influenza' virus strain.

Effects of sex and estrous cycle on sleep and cataplexy in narcoleptic mice.

Narcolepsy type 1 (NT1) is a rare neurology disorder caused by the loss of orexin/hypocretin neurons. NT1 is characterized by excessive daytime sleepiness, sleep and wake fragmentation, and cataplexy. These symptoms have been equally described in both women and men, although influences of gender and hormonal cycles have been poorly studied.

Histamine in murine narcolepsy: What do genetic and immune models tell us?

An increased number of histaminergic neurons, identified by labeling histidine-decarboxylase (HDC) its synthesis enzyme, was unexpectedly found in patients with narcolepsy type 1 (NT1). In quest for enlightenment, we evaluate whether an increase in HDC cell number and expression level would be detected in mouse models of the disease, in order to provide proof of concepts reveling possible mechanisms of compensation for the loss of orexin neurons, and/or of induced expression as a consequence of local neuroinflammation, a state that likely accompanies NT1. To further explore the compensatory hypothesis, we also study the noradrenergic wake-promoting system.

Young Neurons Tickle Memory during REM Sleep.

Memory formation is a dynamic process and sleep is part of it. Consolidation of memories relies on finely orchestrated brain activities occurring during the post-learning sleep period. In this issue of Neuron, Kumar and colleagues provide evidence that the activity of adult-born hippocampal neurons during REM sleep is critical for the consolidation of episodic memory.

Insights into paradoxical (REM) sleep homeostatic regulation in mice using an innovative automated sleep deprivation method.

Identifying the precise neuronal networks activated during paradoxical sleep (PS, also called REM sleep) has been a challenge since its discovery. Similarly, our understanding of the homeostatic mechanisms regulating PS, whether through external modulation by circadian and ultradian drives or via intrinsic homeostatic regulation, is still limited, largely due to interfering factors rendering the investigation difficult. Indeed, none of the studies published so far were able to manipulate PS without significantly altering slow-wave sleep and/or stress level, thus introducing a potential bias in the analyses.

Sub-regions of the dorsal raphé nucleus receive different inputs from the brainstem.

The dorsal raphe nucleus (DRN) through its extensive efferent projections has been implicated in a great variety of physiological and behavioral functions including the regulation of the sleep-wake cycle. This nucleus is composed of five sub-regions defined according to the distribution of its serotonergic (5-HT) neurons. In addition to its heterogeneity in neuronal populations, the DRN contains a great diversity of 5-HT neuronal subtypes identified based on their electrophysiological characteristics, morphology and sub-regional distribution.

The inappropriate occurrence of rapid eye movement sleep in narcolepsy is not due to a defect in homeostatic regulation of rapid eye movement sleep.

Narcolepsy type 1 is a disabling disorder with four primary symptoms: excessive-daytime-sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. The later three symptoms together with a short rapid eye movement (REM) sleep latency have suggested impairment in REM sleep homeostatic regulation with an enhanced propensity for (i.e.

Narcolepsy Type 1 as an Autoimmune Disorder: Evidence, and Implications for Pharmacological Treatment.

Narcolepsy type 1 (NT1) is a rare sleep disorder caused by the very specific loss of hypothalamic hypocretin (Hcrt)/orexin neurons. The exact underlying process leading to this destruction is yet unknown, but indirect evidence strongly supports an autoimmune origin. The association with immune-related genetic factors, in particular the strongest association ever reported in a disease with an allele of a human leukocyte antigen (HLA) gene, and with environmental factors (i.

Mapping the Hypocretin/Orexin Neuronal System: An Unexpectedly Productive Journey.

Early in 1998, we (de Lecea et al., 1998) and others (Sakurai et al., 1998) described the same hypothalamic neuropeptides, respectively called the hypocretins or orexins, which were discovered using two different approaches.

CT scan evaluation of glenoid bone and pectoralis major tendon: interest in shoulder prosthesis.

Introduction: The shoulder arthroplasty brings satisfaction to patients in terms of quality of life and indolence. However whether anatomic implant or reverse, it does not escape from the loosening of the glenoid component. Moreover, optimal implantation is required to ensure the functional outcome without shortening of the arm.

CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice.

Narcolepsy with cataplexy is a rare and severe sleep disorder caused by the destruction of orexinergic neurons in the lateral hypothalamus. The genetic and environmental factors associated with narcolepsy, together with serologic data, collectively point to an autoimmune origin. The current animal models of narcolepsy, based on either disruption of the orexinergic neurotransmission or neurons, do not allow study of the potential autoimmune etiology.

Not a single but multiple populations of GABAergic neurons control sleep.

The role of gamma-amino butyric acid (GABA) in sleep induction and maintenance is well accepted since most insomnia treatments target GABAa receptors. However, the population(s) of GABAergic neurons involved in the beneficial effect of GABA on sleep remains to be identified. This is not an easy task since GABAergic neurons are widely distributed in all brain structures.

The supramammillary nucleus and the claustrum activate the cortex during REM sleep.

Evidence in humans suggests that limbic cortices are more active during rapid eye movement (REM or paradoxical) sleep than during waking, a phenomenon fitting with the presence of vivid dreaming during this state. In that context, it seemed essential to determine which populations of cortical neurons are activated during REM sleep. Our aim in the present study is to fill this gap by combining gene expression analysis, functional neuroanatomy, and neurochemical lesions in rats.

Differential Involvement of the Dentate Gyrus in Adaptive Forgetting in the Rat.

How does the brain discriminate essential information aimed to be stored permanently from information required only temporarily, and that needs to be cleared away for not saturating our precious memory space? Reference Memory (RM) refers to the long-term storage of invariable information whereas Working Memory (WM) depends on the short-term storage of trial-unique information. Previous work has revealed that WM tasks are very sensitive to proactive interference. In order to prevent such interference, irrelevant old memories must be forgotten to give new ones the opportunity to be stabilized.

Chronic Intermittent Hypoxia Induces Chronic Low-Grade Neuroinflammation in the Dorsal Hippocampus of Mice.

Study Objectives: Obstructive sleep apnea (OSA) induces cognitive impairment that involves intermittent hypoxia (IH). Because OSA is recognized as a low-grade systemic inflammatory disease and only some patients develop cognitive deficits, we investigated whether IH-related brain consequences shared similar pathophysiology and required additional factors such as systemic inflammation to develop.

Design: Nine-week-old male C57BL/6J mice were exposed to 1 day, 6 or 24 w of IH (alternating 21-5% FiO2 every 30 sec, 8 h/day) or normoxia.

Paradoxical (REM) sleep deprivation in mice using the small-platforms-over-water method: polysomnographic analyses and melanin-concentrating hormone and hypocretin/orexin neuronal activation before, during and after deprivation.

Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small-platforms-over-water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep.

Hypothalamic immunopathology in anti-Ma-associated diencephalitis with narcolepsy-cataplexy.

Importance: Idiopathic narcolepsy with cataplexy is thought to be an autoimmune disorder targeting hypothalamic hypocretin neurons. Symptomatic narcolepsy with low hypocretin level has been described in Ma antibody–associated encephalitis; however, the mechanisms underlying such an association remain unknown.

Observations: We described a 63-year-old man with clinical criteria for diencephalic encephalitis with sleepiness, cataplexy, hypocretin deficiency, and central hypothyroidism, together with brainstem encephalitis reflected by supranuclear ophtalmoparesis and rapid eye movement sleep behavior disorder with underlying abnormalities on brain magnetic resonance imaging.

Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients' clinical states and may cause lifelong drug dependence.

Brainstem mechanisms of paradoxical (REM) sleep generation.

Paradoxical sleep (PS) is characterized by EEG activation with a disappearance of muscle tone and the occurrence of rapid eye movements (REM) in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Soon after the discovery of PS, it was demonstrated that the structures necessary and sufficient for its genesis are restricted to the brainstem. We review here recent results indicating that brainstem glutamatergic and GABAergic, rather than cholinergic and monoaminergic, neurons play a key role in the genesis of PS.

Melanin concentrating hormone in central hypersomnia.

Background: Narcolepsy with cataplexy (NC) is a disabling disorder characterized by excessive daytime sleepiness and abnormal rapid eye movement (REM) sleep manifestations, due to a deficient hypocretin/orexin neurotransmission. Melanin concentrating hormone (MCH) neurons involved in the homeostatic regulation of REM sleep are intact. We hypothesized that an increased release of MCH in NC would be partly responsible for the abnormal REM sleep manifestations.

The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known.