المؤلفون: Melzi, Silvia, Morel, Anne‐laure, Scoté‐blachon, Céline, Liblau, Roland, Dauvilliers, Yves, Peyron, Christelle

المساهمون: Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), ANR-18-CE17-0014,NARCO-T1,Physiopathologie de la narcolepsie de type 1(2018)

المصدر: ISSN: 1015-6305.

مصطلحات موضوعية: hypocretin, hypothalamus, orexin, sleep, MESH: Animals, MESH: Histamine* / metabolism, MESH: Histidine Decarboxylase / genetics, MESH: Humans, MESH: Mice, MESH: Mixed Function Oxygenases, MESH: Narcolepsy* / genetics, MESH: Narcolepsy* / metabolism, MESH: Orexins / metabolism, MESH: RNA, Messenger, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology

الوصف: International audience ; 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. Immunohistochemistry for HDC, orexin, and melanin-concentrating hormone (MCH) was used to count neurons. Quantitative-PCR of HDC, orexin, MCH, and tyrosine-hydroxylase was performed to evaluate levels of mRNA expression in the hypothalamus or the dorsal pons. Both quantifications were achieved in genetic and neuroinflammatory models of narcolepsy with major orexin impairment, namely the orexin-deficient (Orex-KO) and orexin-hemagglutinin (Orex-HA) mice respectively. The number of HDC neurons and mRNA expression level were unchanged in Orex-KO mice compared to controls. Similarly, we found no change in tyrosine-hydroxylase mRNA expression in the dorsal pons between groups. Further, despite the presence of protracted local neuroinflammation as witnessed by the presence of reactive microglia, we found no change in the number of neurons nor the expression of HDC in Orex-HA mice compared to controls. Importantly, no correlation was found in all conditions between HDC and orexin. Our findings indicate that, in mice, the expression of histamine and noradrenalin, two wake-promoting systems, are not modulated by orexin level whether the lack of orexin is constitutive or induced at adult age, showing thus no compensation. They also show no recruitment of histamine by local neuroinflammation. Further studies will be needed to further define the ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34672414; hal-03443235; https://hal.science/hal-03443235Test; https://hal.science/hal-03443235/documentTest; https://hal.science/hal-03443235/file/bpa.13027.pdfTest; PUBMED: 34672414; PUBMEDCENTRAL: PMC8877734

الإتاحة: https://doi.org/10.1111/bpa.13027Test
https://hal.science/hal-03443235Test
https://hal.science/hal-03443235/documentTest
https://hal.science/hal-03443235/file/bpa.13027.pdfTest

المؤلفون: Pizza, Fabio, Barateau, Lucie, Dauvilliers, Yves, Plazzi, Giuseppe

المساهمون: Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Alma Mater Studiorum Università di Bologna = University of Bologna (UNIBO), Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

المصدر: ISSN: 0962-1105.

مصطلحات موضوعية: Insomnia, Narcolepsy, Orexin/hypocretin, Sleep disturbances, MESH: Animals, MESH: Carrier Proteins, MESH: Cataplexy, MESH: Humans, MESH: Intracellular Signaling Peptides and Proteins, MESH: Narcolepsy, MESH: Orexins, MESH: Sleep, MESH: Wakefulness, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]

الوصف: International audience ; Summary The orexins, also known as hypocretins, are two neuropeptides (orexin A and B or hypocretin 1 and 2) produced by a few thousand neurons located in the lateral hypothalamus that were independently discovered by two research groups in 1998. Those two peptides bind two receptors (orexin/hypocretin receptor 1 and receptor 2) that are widely distributed in the brain and involved in the central physiological regulation of sleep and wakefulness, orexin receptor 2 having the major role in the maintenance of arousal. They are also implicated in a multiplicity of other functions, such as reward seeking, energy balance, autonomic regulation and emotional behaviours. The destruction of orexin neurons is responsible for the sleep disorder narcolepsy with cataplexy (type 1) in humans, and a defect of orexin signalling also causes a narcoleptic phenotype in several animal species. Orexin discovery is unprecedented in the history of sleep research, and pharmacological manipulations of orexin may have multiple therapeutic applications. Several orexin receptor antagonists were recently developed as new drugs for insomnia, and orexin agonists may be the next‐generation drugs for narcolepsy. Given the broad range of functions of the orexin system, these drugs might also be beneficial for treating various conditions other than sleep disorders in the near future.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35698789; hal-04493742; https://hal.science/hal-04493742Test; https://hal.science/hal-04493742/documentTest; https://hal.science/hal-04493742/file/Journal%20of%20Sleep%20Research%20-%202022%20-%20Pizza%20-%20The%20orexin%20story%20sleep%20and%20sleep%20disturbances.pdfTest; PUBMED: 35698789; WOS: 000810296900001

الإتاحة: https://doi.org/10.1111/jsr.13665Test
https://hal.science/hal-04493742Test
https://hal.science/hal-04493742/documentTest
https://hal.science/hal-04493742/file/Journal%20of%20Sleep%20Research%20-%202022%20-%20Pizza%20-%20The%20orexin%20story%20sleep%20and%20sleep%20disturbances.pdfTest

المؤلفون: Boof, Mari-Laure, Ufer, Mike, Fietze, Ingo, Pepin, Jean Louis, Le Guern, Anne-Sophie, Lemoine, Vincent, Dingemanse, Jasper

المساهمون: Idorsia Pharmaceut, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire CHU Grenoble (CHUGA)

المصدر: ISSN: 1550-9389 ; Journal of Clinical Sleep Medicine ; https://hal.science/hal-03679843Test ; Journal of Clinical Sleep Medicine, 2022, 92, pp.4-11. ⟨10.1016/j.sleep.2021.11.015⟩.

مصطلحات موضوعية: Obstructive sleep apnea, Dual orexin receptor antagonist, Daridorexant, Nighttime respiration, Sleep, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology

الوصف: International audience ; Background: The dual orexin receptor antagonist daridorexant did not impact nighttime respiratory function as assessed by the apnea/hypopnea index (AHI) and nocturnal oxygen saturation (SpO2) and improved sleep in patients with mild to moderate obstructive sleep apnea (OSA). These analyses were supplemented with further evaluations of various indices of OSA severity and sleep variables.Methods: In this randomized, double-blind, placebo-controlled, two-period, crossover study, 50 mg daridorexant or placebo was administered every evening for 5 days to 28 patients with mild to moderate OSA. Treatment differences (daridorexant – placebo) were explored for indices of OSA severity including the number and duration of apneas and hypopneas, mean and lowest nocturnal SpO2, sleep duration during each hour of polysomnography recording, and the number and mean and longest duration of awakenings.Results: After repeated-dose daridorexant, more respiratory events were observed compared to placebo, ie., treatment difference of 16.4 events (90% confidence interval: −0.4, 33.2) which is explained by a longer total sleep time. However, no treatment difference was detected for the longest duration of apneas and hypopneas (1.5 s [–8.3, 11.2] and 8.2 s [–6.6, 23.0], respectively), and lowest SpO2 (0.9% [–0.3, 2.1]). The number of awakenings was similar between daridorexant and placebo while daridorexant shortened the longest duration by 16.2 min (8.5, 23.8).Overall, results were similar after single and repeated dosing for both respiratory and sleep aspects.Conclusion: These results suggest safe use of daridorexant in patients with mild to moderate OSA.Clinical trial registration: ClinicalTrials.gov NCT03765294. A study to investigate the effects of ACT-541468 on nighttime respiratory function in patients with mild to moderate obstructive sleep apnea. https://clinicaltrials.gov/ct2/show/NCT03765294Test.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/35306405; hal-03679843; https://hal.science/hal-03679843Test; https://hal.science/hal-03679843/documentTest; https://hal.science/hal-03679843/file/1-s2.0-S1389945722000399-main.pdfTest; PUBMED: 35306405

الإتاحة: https://doi.org/10.1016/j.sleep.2021.11.015Test
https://hal.science/hal-03679843Test
https://hal.science/hal-03679843/documentTest
https://hal.science/hal-03679843/file/1-s2.0-S1389945722000399-main.pdfTest

المؤلفون: Couvineau, Alain, Voisin, Thierry, Nicole, Pascal, Gratio, Valerie, Blais, Anne

المساهمون: Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

المصدر: ISSN: 1007-9327 ; World Journal of Gastroenterology ; https://agroparistech.hal.science/hal-04355985Test ; World Journal of Gastroenterology, 2021, 27, pp.7582 - 7596. ⟨10.3748/wjg.v27.i44.7582⟩.

مصطلحات موضوعية: Alain Couvineau 0000-0003-2912-5168 Thierry Voisin 0000-0002-4320-5183 Pascal Nicole 0000-0002-0004-616X Valerie Gratio 0000-0001-8563-3293 Anne Blais 0000-0002-0897-7612 Invited article Externally peer reviewed Peer-review report's scientific quality classification Grade A (Excellent): 0 Grade B (Very good): 0 Orexin Neuropeptide G-protein coupled receptor superfamily Inflammation Metabolic syndrome Cancer, Alain Couvineau 0000-0003-2912-5168, Thierry Voisin 0000-0002-4320-5183, Pascal Nicole 0000-0002-0004-616X, Valerie Gratio 0000-0001-8563-3293, Anne Blais 0000-0002-0897-7612 Invited article, Externally peer reviewed Peer-review report's scientific quality classification Grade A (Excellent): 0 Grade B (Very good): 0 Orexin, Neuropeptide, G-protein coupled receptor superfamily, Inflammation, Metabolic syndrome, Cancer, [SDV]Life Sciences [q-bio]

الوصف: Hypothalamic neuropeptides named hypocretin/orexins which were identified in 1998 regulate critical functions such as wakefulness in the central nervous system. These past 20 years had revealed that orexins/receptors system was also present in the peripheral nervous system where they participated to the regulation of multiple functions including blood pressure regulation, intestinal motility, hormone secretion, lipolyze and reproduction functions. Associated to these peripheral functions, it was found that orexins and their receptors were involved in various diseases such as acute/chronic inflammation, metabolic syndrome and cancers. The present review suggests that orexins or the orexin neural circuitry represent potential therapeutic targets for the treatment of multiple pathologies related to inflammation including intestinal bowel disease, multiple sclerosis and septic shock, obesity and digestive cancers.

العلاقة: hal-04355985; https://agroparistech.hal.science/hal-04355985Test; https://agroparistech.hal.science/hal-04355985/documentTest; https://agroparistech.hal.science/hal-04355985/file/Orexins%20A%20promising%20target%20to%20digestive%20cancers,%20inflammation,.pdfTest

الإتاحة: https://doi.org/10.3748/wjg.v27.i44.7582Test
https://agroparistech.hal.science/hal-04355985Test
https://agroparistech.hal.science/hal-04355985/documentTest
https://agroparistech.hal.science/hal-04355985/file/Orexins%20A%20promising%20target%20to%20digestive%20cancers,%20inflammation,.pdfTest

المؤلفون: Marraudino, Marilena, Ponti, Giovanna, Moussu, Chantal, Farinetti, Alice, Macchi, Elisabetta, Accornero, Paolo, Gotti, Stefano, Collado, Paloma, Keller, Matthieu, Panzica, Giancarlo

المساهمون: Neuroscience Institute Cavalieri-Ottolenghi, Physiologie de la reproduction et des comportements Nouzilly (PRC), Institut Français du Cheval et de l'Equitation Saumur (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Torino = University of Turin (UNITO), Universidad Nacional de Educación a Distancia (UNED)

المصدر: ISSN: 2218-1989 ; Metabolites ; https://hal.science/hal-03423551Test ; Metabolites, 2021, 11 (7), pp.1-27. ⟨10.3390/metabo11070449⟩.

مصطلحات موضوعية: endocrine disruptor, dimorphism, obesity, kisspeptin, POMC, orexin, phytoestrogens, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism

الوصف: International audience ; The phytoestrogen genistein (GEN) may interfere with permanent morphological changes in the brain circuits sensitive to estrogen. Due to the frequent use of soy milk in the neonatal diet, we aimed to study the effects of early GEN exposure on some physiological and reproductive parameters. Mice of both sexes from PND1 to PND8 were treated with GEN (50 mg/kg body weight, comparable to the exposure level in babies fed with soy-based formulas). When adult, we observed, in GEN-treated females, an advanced pubertal onset and an altered estrous cycle, and, in males, a decrease of testicle weight and fecal testosterone concentration. Furthermore, we observed an increase in body weight and altered plasma concentrations of metabolic hormones (leptin, ghrelin, triiodothyronine) limited to adult females. Exposure to GEN significantly altered kisspeptin and POMC immunoreactivity only in females and orexin immunoreactivity in both sexes. In conclusion, early postnatal exposure of mice to GEN determines long-term sex-specific organizational effects. It impairs the reproductive system and has an obesogenic effect only in females, which is probably due to the alterations of neuroendocrine circuits controlling metabolism; thus GEN, should be classified as a metabolism disrupting chemical

العلاقة: hal-03423551; https://hal.science/hal-03423551Test; https://hal.science/hal-03423551/documentTest; https://hal.science/hal-03423551/file/2021%20Metabolites.pdfTest; WOS: 000676333500001

الإتاحة: https://doi.org/10.3390/metabo11070449Test
https://hal.science/hal-03423551Test
https://hal.science/hal-03423551/documentTest
https://hal.science/hal-03423551/file/2021%20Metabolites.pdfTest

المؤلفون: Melzi, Silvia, Morel, Anne‐Laure, Scoté‐Blachon, Céline, Liblau, Roland, Dauvilliers, Yves, Peyron, Christelle

المساهمون: Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier)

المصدر: ISSN: 1015-6305.

مصطلحات موضوعية: hypocretin, hypothalamus, orexin, sleep, [SDV]Life Sciences [q-bio]

الوصف: International audience ; 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. Immunohistochemistry for HDC, orexin, and melanin-concentrating hormone (MCH) was used to count neurons. Quantitative-PCR of HDC, orexin, MCH, and tyrosine-hydroxylase was performed to evaluate levels of mRNA expression in the hypothalamus or the dorsal pons. Both quantifications were achieved in genetic and neuroinflammatory models of narcolepsy with major orexin impairment, namely the orexin-deficient (Orex-KO) and orexin-hemagglutinin (Orex-HA) mice respectively. The number of HDC neurons and mRNA expression level were unchanged in Orex-KO mice compared to controls. Similarly, we found no change in tyrosine-hydroxylase mRNA expression in the dorsal pons between groups. Further, despite the presence of protracted local neuroinflammation as witnessed by the presence of reactive microglia, we found no change in the number of neurons nor the expression of HDC in Orex-HA mice compared to controls. Importantly, no correlation was found in all conditions between HDC and orexin. Our findings indicate that, in mice, the expression of histamine and noradrenalin, two wake-promoting systems, are not modulated by orexin level whether the lack of orexin is constitutive or induced at adult age, showing thus no compensation. They also show no recruitment of histamine by local neuroinflammation. Further studies will be needed to further define the ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34672414; hal-03443235; https://hal.archives-ouvertes.fr/hal-03443235Test; https://hal.archives-ouvertes.fr/hal-03443235/documentTest; https://hal.archives-ouvertes.fr/hal-03443235/file/bpa.13027.pdfTest; PUBMED: 34672414

الإتاحة: https://doi.org/10.1111/bpa.13027Test
https://hal.archives-ouvertes.fr/hal-03443235Test
https://hal.archives-ouvertes.fr/hal-03443235/documentTest
https://hal.archives-ouvertes.fr/hal-03443235/file/bpa.13027.pdfTest

المؤلفون: Burdakov, Denis, Karnani, Mahesh

المساهمون: Saints-Pères Paris Institute for the Neurosciences

المصدر: ISSN: 2652-1768 ; Neuroanatomy and Behaviour ; https://hal.archives-ouvertes.fr/hal-03246687Test ; Neuroanatomy and Behaviour, 2021, 3, pp.e17. ⟨10.35430/nab.2021.e17⟩.

مصطلحات موضوعية: Lateral hypothalamus, Mating, Orexin, Hypocretin, Calcium imaging, Miniscope, Freely moving recording, Mouse fellatio, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Mating behaviours affect hypothalamic orexin/hypocretin neurons and vice versa. However, activity of orexin neurons has not been recorded during mating before. We report an anecdotal dataset of freely-moving miniature microscope recordings of orexin neuron activity during mating behaviours, as well as an oral sexual encounter previously undocumented in mice. Across the orexin neuron population in the male, firing rates were maximally diverse during ejaculation, similarly diverse though weaker during intromission, and inverse to this during anterior thrusting. In the female mouse, orexin neurons tended to decrease firing during intromission after a transient increase. We provide this brief dataset for re-use, to enable further studies of these rare behaviours with challenging surgical preparations.

العلاقة: hal-03246687; https://hal.archives-ouvertes.fr/hal-03246687Test; https://hal.archives-ouvertes.fr/hal-03246687/documentTest; https://hal.archives-ouvertes.fr/hal-03246687/file/Burdakov%20Karnani%20nab.2021.e17.pdfTest

الإتاحة: https://doi.org/10.35430/nab.2021.e17Test
https://hal.archives-ouvertes.fr/hal-03246687Test
https://hal.archives-ouvertes.fr/hal-03246687/documentTest
https://hal.archives-ouvertes.fr/hal-03246687/file/Burdakov%20Karnani%20nab.2021.e17.pdfTest

المؤلفون: Salvo, Francesco, Micoulaud-Franchi, Jean-Arthur, Palagini, Laura, Geoffroy, Pierre A

المساهمون: Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

المصدر: ISSN: 0160-6689.

مصطلحات موضوعية: Humans, Orexin Receptor Antagonists, Disease Susceptibility, Violence, Suicide, World Health Organization, Orexins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie

الوصف: International audience

العلاقة: hal-04272668; https://hal.science/hal-04272668Test

الإتاحة: https://doi.org/10.4088/JCP.23br14923Test
https://hal.science/hal-04272668Test

المؤلفون: Barateau, Lucie, Dauvilliers, Yves

المساهمون: Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

المصدر: ISSN: 1756-2856.

مصطلحات موضوعية: cataplexy, hypocretin/orexin, immune-based therapies, narcolepsy type 1, narcolepsy type 2, sleepiness, [SCCO]Cognitive science, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]

الوصف: International audience ; Narcolepsy type 1 (NT1) is a chronic orphan disorder, caused by the selective and irreversible loss of hypocretin/orexin (ORX) neurons, by a probable autoimmune process. Little is known about NT2 etiology and prevalence, sharing with NT1 excessive daytime sleepiness (EDS) and dysregulation of rapid eye movement (REM) sleep, but without cataplexy and loss of ORX neurons. Despite major advances in our understanding of the neurobiological basis of NT1, management remains nowadays only symptomatic. The main and most disabling symptom, EDS, is managed with psychostimulants, as modafinil/armodafinil, methylphenidate, or amphetamines as a third-line therapy. Narcolepsy is an active area for drug development, and new wake-promoting agents have been developed over the past years. Pitolisant, a selective histamine H3 receptor inverse agonist, has been recently approved to treat patients with NT1 and NT2. Solriamfetol, a phenylalanine derivative with dopaminergic and noradrenergic activity will be soon a new therapeutic option to treat EDS in NT1 and NT2. Sodium oxybate, used for decades in adult patients with narcolepsy, was recently shown to be effective and safe in childhood narcolepsy. The discovery of ORX deficiency in NT1 opened new therapeutic options oriented towards ORX-based therapies, especially nonpeptide ORX receptor agonists that are currently under development. In addition, immune-based therapies administered as early as possible after disease onset could theoretically slow down or stop the destruction of ORX neurons in some selected patients. Further well-designed controlled trials are required to determine if they could really impact on the natural history of the disease. Given the different clinical, biological and genetic profiles, narcolepsy may provide a nice example for developing personalized medicine in orphan diseases, that could ultimately aid in similar research and clinical efforts for other conditions.

العلاقة: hal-02552181; https://hal.umontpellier.fr/hal-02552181Test; https://hal.umontpellier.fr/hal-02552181/documentTest; https://hal.umontpellier.fr/hal-02552181/file/1756286419875622.pdfTest

الإتاحة: https://doi.org/10.1177/1756286419875622Test
https://hal.umontpellier.fr/hal-02552181Test
https://hal.umontpellier.fr/hal-02552181/documentTest
https://hal.umontpellier.fr/hal-02552181/file/1756286419875622.pdfTest

المؤلفون: Loiseau, Camille, Casciato, Alexis, Barka, Besma, Cayetanot, Florence, Bodineau, Laurence

المساهمون: Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU)

المصدر: ISSN: 1664-042X ; Frontiers in Physiology ; https://hal.sorbonne-universite.fr/hal-02315133Test ; Frontiers in Physiology, 2019, 10, ⟨10.3389/fphys.2019.01200⟩.

مصطلحات موضوعية: CO 2 /H + chemosensitivity, congenital central hypoventilation syndrome, etonogestrel, ex vivo central nervous system preparation, orexin, progestin, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Dysfunction of central respiratory CO2/H+ chemosensitivity is a pivotal factor that elicits deep hypoventilation in patients suffering from central hypoventilation syndromes. No pharmacological treatment is currently available. The progestin desogestrel has been suggested to allow recovery of respiratory response to CO2/H+ in patients suffering from central hypoventilation, but except the fact that supramedullary regions may be involved, mechanisms are still unknown. Here, we tested in neonates whether orexin systems contribute to desogestrel’s central effects on respiratory function. Using isolated ex vivo central nervous system preparations from newborn rats, we show orexin and almorexant, an antagonist of orexin receptors, supressed strengthening of the increase in respiratory frequency induced by prolonged metabolic acidosis under exposure to etonogestrel, the active metabolite of desogestrel. In parallel, almorexant suppressed the increase and enhanced increase in c-fos expression in respiratory-related brainstem structures induced by etonogestrel. These results suggest orexin signalisation is a key component of acidosis reinforcement of respiratory drive by etonogestrel in neonates. Although stage of development used is different as that for progestin clinical observations, presents results provide clues about conditions under which desogestrel or etonogestrel may enhance ventilation in patients suffering from central hypoventilation syndromes.

العلاقة: hal-02315133; https://hal.sorbonne-universite.fr/hal-02315133Test; https://hal.sorbonne-universite.fr/hal-02315133/documentTest; https://hal.sorbonne-universite.fr/hal-02315133/file/fphys-10-01200.pdfTest

الإتاحة: https://doi.org/10.3389/fphys.2019.01200Test
https://hal.sorbonne-universite.fr/hal-02315133Test
https://hal.sorbonne-universite.fr/hal-02315133/documentTest
https://hal.sorbonne-universite.fr/hal-02315133/file/fphys-10-01200.pdfTest