Fixing the Broken Clock: Optogenetic methods to restore circadian rhythms in a mouse model of Alzheimer’s Disease

2015 Pilot Project Read More

Investigators

Principal Investigator: Erik Musiek (WUSTL Neurology)
Collaborators: Erik Herzog (WUSTL Biology) and Geraldine Kress (WUSTL Neurology)

Description

Disturbances of the sleep-wake cycle and circadian rhythms, the 24-hour oscillations which govern many aspects of bodily function, are associated with aging and are common in many neurodegenerative diseases, including Alzheimer’s Disease (AD). Emerging evidence strongly suggests that disrupted sleep and circadian rhythms can lead to increased accumulation of amyloid-beta (Aβ), a peptide key to the pathogenesis of AD. Aβ levels in the brain also show a clear day-night rhythm which is tied to the sleep/wake cycle. Circadian and sleep rhythms are generated by the master clock of the body, the suprachiasmatic nucleus (SCN) of the hypothalamus. SCN function declines with age in mice and humans, leading to disrupted rhythms. While age- and disease-related declines in sleep and circadian function have been hypothesized to contribute to neurodegeneration, no methods to specifically manipulate these circadian rhythms have been available. We propose to use optogenetics, a method of stimulating neuronal activity in the brain using light, to stimulate or suppress neurons in the SCN of mouse models of AD. We will determine if acutely altering the firing of the SCN, and thus the circadian rhythms of the animal, can change the dynamics of Aβ levels in the brain. We will also determine if properly-timed optogenetic activation of SCN can rejuvenate the impaired circadian rhythms in mouse models of AD. We hope to create a novel method of “fixing the broken clock” which can be applied across neurodegenerative disease models, in order to understand how circadian function impacts neurodegeneration.

Investigators

Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Erik Musiek

Erik Herzog

Support

This pilot project is made possible by the Danforth Foundation Challenge Endowment.

Danforth Challenge Endowment