التفاصيل البيبلوغرافية
| العنوان: |
Orexin / hypocretin deficiency in humans : consequences and pathophysiology, Narcolepsy Type 1 as an experimental model ; Déficience en orexine, hypocrétine chez l’homme : conséquences et pathophysiologie, la Narcolepsie de Type 1 comme modèle expérimental |
| المؤلفون: |
Barateau, Lucie |
| المساهمون: |
Montpellier, Dauvilliers, Yves |
| المصدر: |
Theses.fr |
| سنة النشر: |
2019 |
| مصطلحات موضوعية: |
Narcolepsie de type 1, Hypocrétine/orexine, Dysautonomie, Auto-Immunité, Psychiatrie, Biomarqueurs, Narcolepsy type 1, Hypocretin/orexin, Dysautonomia, Auto-Immunity, Psychiatry, Biomarkers, psy, socio |
| الوصف: |
Orexin-A (ORX) and -B (or hypocretins 1 and -2) are hypothalamic neuropeptides discovered two decades ago. In humans, the selective destruction of ORX neurons leads to narcolepsy type 1 (NT1), a rare sleep disease characterized by excessive daytime sleepiness, cataplexy, fragmented nocturnal sleep, and abnormal expressions of rapid eye movement (REM) sleep. ORX plays a major role in sleep and wake regulation, but also neuroendocrine and autonomic functions, motor control, motivated behaviors, and reward seeking. This thesis explores the consequences and pathophysiology of ORX deficiency in humans, considering NT1 as an experimental model. The 1st part focuses on dysautonomia in NT1. We assessed systematically autonomic impairment, in a large cohort of NT1, using the SCOPA-AUT questionnaire (Clinical autonomic dysfunction in NT1, Sleep 2019). We explored MIBG cardiac scintigraphy in NT1, and showed an absence of cardiac sympathetic denervation (CSD), but a link with REM sleep motor deregulation (Exploration of cardiac sympathetic adrenergic nerve activity in narcolepsy, Clinical Neurophysiology 2018). Idiopathic REM sleep behavior disorder (iRBD) is a parasomnia associated with CSD. RBD is also reported in half of NT1, however MIBG uptake differences were found between NT1 with RBD and iRBD patients (Cardiac sympathetic activity differentiates Idiopathic and symptomatic RBD, Scientific Reports 2018). The 2nd part focuses on the pathophysiological mechanisms in NT1 and therapeutic implications. NT1 has a probable autoimmune (AI) origin, environmental factors interacting with susceptibility genes. However, its pathophysiology is unique, and we showed no specific association with other immune-based disorders in NT1 in contrast to many other AI diseases (Comorbidity between central disorders of hypersomnolence and immune-based disorders, Neurology 2017). The loss of ORX neurons is irreversible, but immune-based therapies could prevent their destruction if given close to disease onset. Some neuroinflammatory disorders ... |
| نوع الوثيقة: |
thesis |
| اللغة: |
English |
| العلاقة: |
10670/1.vpmg57; http://www.theses.fr/2019MONTT042Test |
| الإتاحة: |
http://www.theses.fr/2019MONTT042Test |
| رقم الانضمام: |
edsbas.A5683BFD |
| قاعدة البيانات: |
BASE |
