Sleep Regulation in the Genetic Mouse Model for Fatal Familial Insomnia

• Applicant: Dr. Lars Dittrich
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 274974136

Recent findings imply that healthy sleep is highly important for physical and mental health, particularly as a protective factor against neurodegenerative diseases like Alzheimer´s. The growing recognition of the importance of sleep is contrasted by our insufficient knowledge of its neuronal regulation. This is illustrated by fatal familial insomnia (FFI). FFI is a hereditary prion disease with abrupt onset at midlife. Affected individuals completely lose restorative sleep and die within months to a few years. Current models of sleep regulation cannot explain this unparalleled loss of the ability to sleep. Currently available sleep medication is largely ineffective in FFI patients. A better understanding of the neuropathological mechanisms of FFI is expected to improve our general understanding of sleep regulation and is necessary to improve treatment for FFI patients and possibly also patients with more common sleep pathologies. Progress in FFI research has been hampered by the lack of appropriate animal models. Recently, a knock-in mouse model was introduced as the first genetic animal model for the disease. To date, it is not known whether this mouse replicates the pronounced sleep disruption present in human patients. This project aims to thoroughly characterize the sleep phenotype of the FFI mouse and its ability to respond to experimental challenges to the sleep-homeostatic system, using electroencephalographic/electromyographic (EEG/EMG) recordings. Further, effects of the FFI-mutation on the function of sleep-wake regulatory brain regions will be assessed using Fos immunohistochemistry. Comparison of the FFI mouse with wild type controls as well as prion knock-out mice will allow differentiating between loss-of-function and gain-of-function effects of the mutation.

• DFG Programme: Research Grants
• Co-Investigator: Dr. Walker Jackson, Ph.D.