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La narcolepsie de type 1 : une pathologie du sommeil paradoxal ?

Abstract : Narcolepsy type 1 (NT1) is a rare neurological disease characterized by an excessive daytime sleepiness and episodes of cataplexy – a sudden loss of muscular tone triggered by strong emotions during wakefulness. In humans, NT1 is due to the specific and postnatal loss of orexin (Orex) neurons involved in wake promotion. It led to describe NT1 as a wake disease. However, clinical observations have suggested a disrupted regulation of paradoxical (or REM) sleep in narcolepsy. Indeed, NT1 patients have shorter latency to enter REM sleep and frequent sleep onset in REM sleep. More, muscular atonia observed in cataplexy is one of the main feature of REM sleep. Together, those data led to the hypothesis that narcolepsy would be also a REM sleep disease. We’ve investigated this hypothesis in two different studies performed on a recognize model of murine narcolepsy: the Orex-KO mouse. In a 1st study, we found that despite an intact REM sleep homeostasic regulation, Orex-KO mice had an increased REM sleep propensity during active phase. We’ve suggested a new role of REM sleep inhibition for the neuropeptide Orex. Then, we aimed to determine whether REM sleep atonia and cataplexy shared the same neuronal network. In contrast to the currently admitted hypothesis, we demonstrate that glutamatergic neurons of the sublaterodorsal nucleus (SLD) are not sufficient to generate cataplexy, and are only partially involved in this symptom. Taken together, data harvested during this thesis help us to better understand the role of Orex in NT1 and to improve our knowledge about the neurobiological mechanisms of cataplexy
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Alexis Roman. La narcolepsie de type 1 : une pathologie du sommeil paradoxal ?. Neurosciences. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1329⟩. ⟨tel-02412882⟩

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