Role of Tau Protein in Remodeling of Circadian Neuronal Circuits and Sleep

• Published in: Frontiers in aging neuroscience Vol. 11; p. 320
• Main Authors: Arnes, Mercedes, Alaniz, Maria E, Karam, Caline S, Cho, Joshua D, Lopez, Gonzalo, Javitch, Jonathan A, Santa-Maria, Ismael
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 21.11.2019; Frontiers Media S.A
• Subjects: Axonal plasticity; Behavior; Behavioral plasticity; Biological clocks; Circadian rhythm; Circadian rhythms; Cognitive ability; Cytoskeleton; Disease; Drosophila; Gene expression; Humidity; Insects; Kinases; Molecular modelling; Neural networks; Neurodegeneration; Neurodegenerative diseases; Neurons; Neuroscience; PDF; Proteins; Sleep; Software; structural plasticity; Surgeons; tau; Tau protein; New York; United States > US; sleep; structural plasticity; tau; PDF; circadian rhythm
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2019.00320

Multiple neurological, physiological, and behavioral functions are synchronized by circadian clocks into daily rhythms. Neurodegenerative diseases such as Alzheimer's disease and related tauopathies are associated with a decay of circadian rhythms, disruption of sleep patterns, and impaired cognitive function but the mechanisms underlying these alterations are still unclear. Traditional approaches in neurodegeneration research have focused on understanding how pathology impinges on circadian function. Since in Alzheimer's disease and related tauopathies tau proteostasis is compromised, here we sought to understand the role of tau protein in neuronal circadian biology and related behavior. Considering molecular mechanisms underlying circadian rhythms are conserved from to humans, here we took advantage of a recently developed tau-deficient line to show that loss of tau promotes dysregulation of daily circadian rhythms and sleep patterns. Strikingly, tau deficiency dysregulates the structural plasticity of the small ventral lateral circadian pacemaker neurons by disrupting the temporal cytoskeletal remodeling of its dorsal axonal projections and by inducing a slight increase in the cytoplasmic accumulation of core clock proteins. Taken together, these results suggest that loss of tau function participates in the regulation of circadian rhythms by modulating the correct operation and connectivity of core circadian networks and related behavior.