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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Aging Neurosci. | doi: 10.3389/fnagi.2019.00320

Role of tau protein in remodeling of circadian neuronal circuits and sleep

 Mercedes Arnes1, Maria E. Alaniz1,  Caline S. Karam2, Joshua D. Cho1,  Gonzalo Lopez3, Jonathan A. Javitch4 and  Ismael Santa-Maria1, 5*
  • 1Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, United States
  • 2Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, United States
  • 3Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, United States
  • 4Department of Recreation Therapy, New York State Psychiatric Institute, United States
  • 5Columbia University, United States

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 underlaying 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 Drosophila to humans, here we took advantage of a recently developed tau-deficient Drosophila 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.

Keywords: tau, Circadian Rhythm, Sleep, PDF, structural plasticity

Received: 07 Aug 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Arnes, Alaniz, Karam, Cho, Lopez, Javitch and Santa-Maria. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Ismael Santa-Maria, Columbia University, New York City, United States, is2395@cumc.columbia.edu