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Publication : Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.

First Author  Kang JE Year  2009
Journal  Science Volume  326
Issue  5955 Pages  1005-7
PubMed ID  19779148 Mgi Jnum  J:154074
Mgi Id  MGI:4367168 Doi  10.1126/science.1180962
Citation  Kang JE, et al. (2009) Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326(5955):1005-7
abstractText  Amyloid-beta (Abeta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Abeta aggregation is a concentration-dependent process that is likely responsive to changes in brain interstitial fluid (ISF) levels of Abeta. Using in vivo microdialysis in mice, we found that the amount of ISF Abeta correlated with wakefulness. The amount of ISF Abeta also significantly increased during acute sleep deprivation and during orexin infusion, but decreased with infusion of a dual orexin receptor antagonist. Chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Abeta plaque formation in amyloid precursor protein transgenic mice. Thus, the sleep-wake cycle and orexin may play a role in the pathogenesis of Alzheimer's disease.
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