Disruption of normal circadian clock function in a mouse model of tauopathy.

Disruption of normal circadian clock function in a mouse model of tauopathy. Exp Neurol. 2017 Apr 28;: Authors: Stevanovic K, Yunus A, Joly-Amado A, Gordon M, Morgan D, Gulick D, Gamsby J Abstract Disruption of normal circadian rhythm physiology is associated with neurodegenerative disease. In Alzheimer's disease (AD), circadian dysfunction has been attributed to β-amyloidosis. However, it is presently unclear whether tauopathy, another AD-associated neuropathology, also contributes to the disruption of normal circadian clock function. We demonstrate changes in normal circadian clock function in a transgenic mouse model of tauopathy (Tg4510) through assessment of both molecular and behavioral rhythms. We show that Tg4510 mice display a long free-running period at an age when tauopathy is present, and with corresponding evidence of tauopathy in the suprachiasmatic nucleus (SCN) of the hypothalamus, the site of the master clock. Additionally, we show a disruption in the cyclic expression of the core clock protein PER2 in the hypothalamus. Finally, we observe a disruption in the cyclic expression of PER2 and BMAL1, another core clock protein, in the Tg4510 hippocampus. These results demonstrate that tauopathy disrupts normal circadian clock function at both behavioral and molecular levels, and this disruption may be attributed to tauopathy-induced neuropathology in the SCN. PMID: 28461004 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research