Loss of glia-neuronal interactions and age-dependent cell death in aDrosophilamodel of adult neurodegeneration

Abstract

AbstractWhile glial dysfunction has been implicated in the development of multiple neurodegenerative diseases, the role of glial cell morphology in neurodegeneration is underexplored. In the fruit flyDrosophila melanogaster, mutants of the genedrop-dead(drd) exhibit adult neurodegeneration and extremely short lifespans. The morphology of one class of glia, the cortex glia (CG), is abnormal indrdmutants. In controls, the CGs form a continuous network that wraps around all neuronal cell bodies, but indrdmutants, individual CGs are stunted and the CG network is disrupted. These phenotypes are present on the first day of adulthood. Apoptosis is the central mechanism of cell death indrdmutants; widespread cell death is observed on the first day of adulthood and increases with age and is primarily neuronal. Apoptotic cells are found both within and outside of the remaining CG network, with significant variation in the distribution among individual brains. The degree of cell death and CG network breakdown in young adults could explain whydrdmutant flies die within the first week of adulthood. TheDrosophila drdmutant is a unique model of adult neurodegeneration that provides new insight into the breakdown in interaction between glia and neuronal cell bodies.