Sleep Regulates Glial Plasticity and Expression of the Engulfment Receptor Draper Following Neural Injury

Abstract

Chronic sleep disturbance is associated with numerous health consequences, including neurodegenerative disease and cognitive decline [1]. Neurite damage due to apoptosis, trauma, or genetic factors is a common feature of aging, and clearance of damaged neurons is essential for maintenance of brain function. In the central nervous system, damaged neurites are cleared by Wallerian degeneration, in which activated microglia and macrophages engulf damaged neurons [2]. The fruit fly Drosophila melanogaster provides a powerful model for investigating the relationship between sleep and Wallerian degeneration [3]. Several lines of evidence suggest that glia influence sleep duration, sleep-mediated neuronal homeostasis, and clearance of toxic substances during sleep, raising the possibility that glial engulfment of damaged axons is regulated by sleep [4]. To explore this possibility, we axotomized olfactory receptor neurons and measured the effects of sleep loss or gain on the clearance of damaged neurites. Mechanical and genetic sleep deprivation impaired the clearance of damaged neurites. Conversely, treatment with the sleep-promoting drug gaboxadol accelerated clearance, while genetic induction of sleep promotes Draper expression. In sleep-deprived animals, multiple markers of glial activation were delayed, including activation of the JAK-STAT pathway, upregulation of the cell corpse engulfment receptor Draper, and innervation of the antennal lobe by glial membranes. These markers were all enhanced following genetic and pharmacological sleep induction. Taken together, these findings reveal a critical association between sleep and glial activation following neural injury, providing a platform for further investigations of the molecular mechanisms underlying sleep-dependent modulation of glial function and neurite clearance.

Keywords: Drosophila; microglia; neurodegeneration; olfaction; sleep.