Precise measurement of motor neuron dysfunction in Drosophila ALS model via climbing assay and leg imaging.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disorder characterized by progressive degeneration of motor neurons, leading to muscle weakness, paralysis, and death. While there is a plethora of studies focusing on many aspects of ALS, the pathogenesis of this disease is not well understood, and effective treatments are scarce. Drosophila melanogaster is a powerful model organism for studying ALS due to its genetic tractability and its evolutionarily conserved cellular and molecular processes which are also shared between the fly and human. Here, we introduce two simple and cost-effective methodologies for assessing motor neuron dysfunction in Drosophila: (1) Fast Inexpensive Climbing Test (FICT), and (2) Economical Leg Fluorescence Imaging (ELFI). These methods are established based on using basic equipment and straightforward procedures, making them accessible and applicable in various research and educational settings. FICT provides a non-invasive and high-throughput measure of motor dysfunction, while ELFI allows for direct visualization of fluorescently labeled cells in the Drosophila leg, facilitating the study of cell-cell communications in vivo. Our approach emphasizes the importance of both neuronal and glial contributions to ALS pathogenesis, offering valuable insights for the development of novel therapeutic strategies. These methods democratize access to ALS research tools, promoting global scientific collaboration and advancing our understanding of this devastating disease.