2022.05.11
A quantitative model of sporadic axonal degeneration in the Drosophila visual system
J Neurosci. 2022 May 9:JN-RM-2115-21. doi: 10.1523/JNEUROSCI.2115-21.2022. Online ahead of print.
Richard M1, Doubková K1, Nitta Y2, Kawai H3, Sugie A2, Tavosanis G1,4.
1Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE), 53127 Bonn, Germany.
2Brain Research Institute, Niigata University
3LPIXEL Inc., 100-0004, Tokyo, Japan.
4LIMES Institute, University of Bonn, 53115 Bonn, Germany.
Abstract
In human neurodegenerative diseases, neurons undergo axonal degeneration months to years before they die. Here, we developed a system modelling early degenerative events in Drosophila adult photoreceptor cells. Thanks to the stereotypy of their axonal projections, this system delivers quantitative data on sporadic and progressive axonal degeneration of photoreceptor cells. Using this method, we show that exposure of adult female flies to a constant light stimulation for several days overcomes the intrinsic resilience of R7 photoreceptors and leads to progressive axonal degeneration. This was not associated with apoptosis. We furthermore provide evidence that loss of synaptic integrity between R7 and a postsynaptic partner preceded axonal degeneration, thus recapitulating features of human neurodegenerative diseases. Finally, our experiments uncovered a role of postsynaptic partners of R7 to initiate degeneration, suggesting that postsynaptic cells signal back to the photoreceptor to maintain axonal structure. This model can be used to dissect cellular and circuit mechanisms involved in the early events of axonal degeneration, allowing for a better understanding of how neurons cope with stress and lose their resilience capacities.
*Reprinted under the terms of the Creative Commons Attribution License (CC BY).
