Poster abstracts
Poster number 1 submitted by Nicklaus Halloy
Circadian Timing in PS19 Mouse Model of Tau Pathology
Nicklaus R. Halloy (Neuroscience Graduate Program, The Ohio State University), Megan Formanowicz (Department of Neuroscience, The Ohio State University), Cassie Pham (Department of Neuroscience, The Ohio State University), Kari R. Hoyt (Division of Pharmaceutics & Pharmacology, The Ohio State University), Karl Obrietan (Department of Neuroscience, The Ohio State University)
Abstract:
Circadian disruptions are prevalent in Alzheimer’s Disease (AD), and, as one of the pathological hallmarks of AD, the misfolding and aggregation of tau protein into neurofibrillary tangles may play an integral role. The suprachiasmatic nucleus (SCN) serves as the principal circadian pacemaker, and recent work has indicated disruptions in timing properties in AD. The mechanism by which disruption of SCN clock physiology occurs in AD has yet to be fully elucidated. Thus, investigation of the impact on clock timing of tau pathology is an area of significant interest. Towards this end, the PS19 transgenic mouse line (Prnp-huMAPT*P301S) was employed; it exhibits a fivefold increase in mutant human tau expression compared to endogenous mouse tau. PS19 mice exhibit increased gliosis and synaptic loss at three months-of-age and neurofibrillary tangles by six months. Male PS19 (n = 8, 2.7 ± 0.1 months) and WT (n = 8, 2.8 ± 0.1 months) mice were singly housed in cages equipped with running wheels and were subjected to a battery of assays to assess inherent clock timing and clock entrainment. At 3 months-of-age, PS19 mice showed a trending increase in sensitivity to light re-entrainment during a 6h phase advance, U = 15, p = .081. At 5 months, PS19 mice showed increased average activity compared to WT during constant light, t(14) = 2.66, p = .019. There were no differences in daily activity nor differences in the inherent pacemaker of the animals, indicating core clock timing is not affected. These data suggest that there is a heightened sensitivity to light resulting from tau pathology which could contribute to disruption of the sleep-wake cycle observed in patients with AD. This study is ongoing; it will include female mice and additional experiments to assess circadian timing properties and effects of tau pathology progression in aged animals.
Keywords: circadian, tauopathy, SCN