Variation in serotonergic and dopaminergic neuronal survival in the adult Drosophila CNS

Loss of serotonergic and dopaminergic neurons may have serious implications for normal brain function. Drosophila models of neurodegenerative diseases utilize the short lifespan and simple anatomy of the fly to characterize the molecular and genetic processes characteristic to each dysfunctional state. In fly embryonic and larval ventral nerve cords, serotonergic and dopaminergic neurons are positioned in a stereotypic pattern which is reorganized during metamorphosis. In this study, we examine the adult pattern of serotonergic and dopaminergic neurons within the adult fly ventral nerve cord. We find that the number of cells lost following metamorphosis is highly variable. Changes in cell number due to age is therefore likely to be highly masked by developmental variation. The source of this variation is likely to be apoptosis-based cell loss during pupal development. Sykes 3 Dopaminergic and serotonergic neurons are involved in numerous human disease states, including Parkinson's disease, depression and anxiety. These neurons are subject to age-related changes that may have pathological consequences: in the rat, serotonergic fibers develop aberrant branching patterns, and the entire density of serotonergic fibers in the brain is decreased with age (Nishimura et al., 1998). Similarly, the incidence of Parkinson's disease in humans increases with age, presumably as dopaminergic neurons are lost to neurodegenerative processes (Dauer and Przedborski, 2003). Model systems, such as the fruit fly, provide an opportunity to dissect the molecular and genetic pathways that contribute to proper function of an organism, as well as those pathways that dysfunction in human disease states. Several fly models of human neurodegenerative diseases have been described, including Parkinson's disease, Alzheimer's disease and polyglutamine disease (Chan and Bonini, 2000). Recent studies have specifically targeted fly dopaminergic neurons to model the influence of genes implicated in Parkinson's Disease, such as α-synuclein and Parkin (Feany and Bender, 2000; Yang et al., 2003). Developmentally, the major reorganization of the fly brain during metamorphosis typically spares most cell bodies (White and Kankel, 1978), but may drastically modify the connectivity of the neurons (Technau and Heisenberg, 1982). Furthermore, aging and experience modify nerve fiber density within the fly brain as adult flies mature (Technau 1984). However, in the young adult fly, specific cell clusters of catecholaminergic neurons show variation between individuals upon eclosion (Budnik and White, 1988). Following pupation, a subset of about 300 fly neurons undergo programmed cell death in response to changes in ecdysone levels coincident with eclosion (Robinow et al., 1993). Previous …