Defining the effects of the sleep-wake cycle on astrocyte phenotypes

Recent research has shown an important role for sleep in the clearance of Alzheimer’s disease associated substrates, such as tau and amyloid beta. Astrocytes in the brain are thought to be important in this process, however, the influence of different component of the sleep-wake cycle on astrocyte status has not been investigated.

Aims

To evaluate astrocyte phenotypes in mice during different vigilance states dominated by either wake, NREM or REM sleep

This project therefore evaluates astrocytic phenotypes in mice during different vigilance states dominated by either wake, NREM or REM sleep. The goal of this project is to define how astrocytes are influenced by the different sleep/wake vigilance states in normal animals. Human-tau transgenic and control mice will be surgically implanted with electroencephalogram/electromyogram (EEG/EMG) head-mounts.

After recovery, mice will be dosed during the dark (active) phase with different hypnotic drugs that induce sleep, but with a different balance of REM versus NREM sleep. Control mice are dosed with the inactive vehicle, representing the “awake” group. During the associated NREM, REM or wake-dense periods, mouse brains are harvested. Brains will be assessed by: transcriptomics on immunopan-extracted astrocytes; immunohistochemistry for the assessment of tau and the localisation of astrocytic water channels, and; in situ-hybridisation to determine the localization of astrocyte genes altered by sleep states with candidate genes selected from the transcriptome analysis.

The student will learn about current theories underlying AD, tauopathy, sleep/wake physiology and astrocyte biology. Techniques include transgenic mouse lines, EEG/EMG surgery, analysis of sleep-wake vigilance states, immunopanning, immunohistochemistry and transcriptomic profiling.