Sleep is bi-directionally modified by amyloid beta oligomers

Disrupted sleep is a major feature of Alzheimer's disease (AD), often arising years before symptoms of cognitive decline. Prolonged wakefulness exacerbates the production of amyloid-beta (Aβ) species, a major driver of AD progression, suggesting that sleep loss further accelerates AD through a vicious cycle. However, the mechanisms by which Aβ affects sleep are unknown. We demonstrate in zebrafish that Aβ acutely and reversibly enhances or suppresses sleep as a function of oligomer length. Genetic disruptions revealed that short Aβ oligomers induce acute wakefulness through Adrenergic receptor b2 (Adrb2) and Progesterone membrane receptor component 1 (Pgrmc1), while longer Aβ forms induce sleep through a pharmacologically tractable Prion Protein (PrP) signaling cascade. Our data indicate that Aβ can trigger a bi-directional sleep/wake switch. Alterations to the brain's Aβ oligomeric milieu, such as during the progression of AD, may therefore disrupt sleep via changes in acute signaling events

The prevalence of childhood psychopathology in Turkey: a cross-sectional multicenter nationwide study (EPICPAT-T)

PMID = 3096438

Inhibition of fatty acid oxidation enhances oxidative protein folding and protects hepatocytes from endoplasmic reticulum stress

The unfolded protein response regulates lipid metabolism, but the functional benefit of this regulation to ER function is not clear. This work shows that inhibition of fatty acid oxidation raises cellular oxidation potential, facilitates ER oxidative folding, and protects hepatocytes from ER stress