Loss of glia-neuronal interactions and age-dependent cell death in a Drosophila model of adult neurodegeneration

While 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 fly Drosophila melanogaster, mutants of the gene drop-dead (drd) exhibit adult neurodegeneration and extremely short lifespans. The morphology of one class of glia, the cortex glia (CG), is abnormal in drd mutants. In controls, the CGs form a continuous network that wraps around all neuronal cell bodies, but in drd mutants, 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 in drd mutants; 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 why drd mutant flies die within the first week of adulthood. The Drosophila drd mutant is a unique model of adult neurodegeneration that provides new insight into the breakdown in interaction between glia and neuronal cell bodies.