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maladies neurodégénératives et sommeil

La revue Nature Reviews Neuroscience (10, 764 (November 2009http://www.nature.com/nrn/journal/v10/n11/full/nrn2742.html#top) publie un article focus sur une étude parue dans la revue Science concernant l’incidence du  sommeil et de sa privation sur la formation de plaques amyloïde dans le cadre de l’exploration des maladies dégénératives. Si le sommeil peut ralentir la progression de ces plaques, la maîtrise du niveau des hormones neuronales polypeptidiques notamment, parce qu’elles stimulent l’état d’éveil, doit être envisagée, en ce qu'elle pourrait favoriser la prévention de la démence, chez les individus à risque.


"Neurodegenerative disease: Sleeping away amyloid plaques? Leonie Welberg

Aggregation of extracellular amyloid- (A) is thought to play a major part in the pathogenesis of Alzheimer's disease. Amyloid plaques form when levels of the monomeric, soluble A peptide build up in the interstitial fluid (ISF) in the brain. Holtzman and colleagues now show that orexin influences ISF A levels by regulating the sleep–wake cycle.

The authors used microdialysis to measure ISF A levels in the hippocampus of wild-type mice and transgenic mice that are used as a model of Alzheimer's disease. A diurnal fluctuation in ISF A levels, with higher levels during waking and lower levels during sleep, was detected in both sets of mice and in healthy humans, indicating that it results from a normal regulatory process. In the transgenic mice the levels correlated with the amount of time spent awake.

Housing mice under constant light did not abolish the sleep–wake cycle or the fluctuations in A levels. By contrast, subjecting mice to sleep deprivation increased ISF A levels relative to the normal concentration during the light period, and A levels decreased as soon as the animals fell asleep. These findings indicate that the regulation of ISF A levels is coupled to the sleep–wake cycle rather than to light or dark exposure.

As orexin is a major regulator of sleep and wakefulness, the authors examined whether this neuropeptide also mediates the diurnal fluctuations in ISF A. Intracerebroventricular infusion of orexin for 6 h at the beginning of the light period (when A concentrations are normally low and mice asleep) increased both ISF A levels and wakefulness. Conversely, continuous administration of an orexin receptor antagonist for 24 h by microdialysis reduced wakefulness and overall ISF A levels and abolished the diurnal A fluctuations. The diurnal rhythm was restored immediately upon removal of the antagonist. Together, these findings suggest that orexin signalling regulates ISF A levels.

The finding that the sleep–wake cycle regulates A levels raises the question of whether chronic sleep deprivation can cause A accumulation in the brain. The authors showed that, in transgenic mice, sleep deprivation resulted in greater A plaque deposition than in non-sleep-deprived controls. Importantly, systemic administration of the orexin receptor antagonist decreased plaque formation in several brain regions.

This study shows that orexin signalling and sleep–wake behaviour regulate the level of soluble A in the ISF, and that manipulating either of them can influence A plaque formation in a mouse model of Alzheimer's disease. Interestingly, sleep disturbances are common in people with neurodegenerative disorders. Future studies may therefore investigate whether improving sleep patterns or manipulating orexin levels in individuals at risk for Alzheimer's disease could slow the formation of amyloid plaques and ultimately dementia."


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