Octopamine Drives Endurance Exercise Adaptations in Drosophila

Abstract

Summary Endurance exercise is an effective therapeutic intervention with substantial pro-healthspan effects. Male Drosophila respond to a ramped daily program of exercise by inducing conserved physiological responses similar to those seen in mice and humans. Female flies respond to an exercise stimulus, but do not experience the adaptive training response seen in males. Here, we use female flies as a model to demonstrate that differences in exercise response are mediated by differences in neuronal activity. The activity of octopaminergic neurons is specifically required to induce the conserved cellular and physiological changes seen following endurance training. Furthermore, either intermittent, scheduled activation of octopaminergic neurons, or octopamine feeding, is able to fully substitute for exercise, conferring a suite of pro-healthspan benefits to sedentary Drosophila. These experiments indicate that octopamine is a critical mediator of adaptation to endurance exercise in Drosophila.

Drosophila tafazzinmutants have impaired exercise capacity

“…Wild‐type flies consistently respond to a 3‐week exercise program with improvements to endurance and flight performance (Sujkowski et al. , ). After 3 weeks of endurance exercise training, TAZ mutants ( TAZ −/− EX) did not run significantly longer than unexercised mutant controls ( TAZ −/− UN) (Fig.…”

“…Typically, exercise improves ability to resist cardiac pacing stress (Sujkowski et al. , ). However, after endurance exercise training, exercised TAZ mutants and unexercised TAZ mutants displayed similar failure rate, indicating no resistance to cardiac pacing was gained from endurance training (Fig.…”

“…5C). Typically, exercise improves ability to resist cardiac pacing stress (Sujkowski et al 2015(Sujkowski et al , 2017. However, after endurance exercise training, exercised TAZ There was no significant difference in percent failure between TAZ +/+ flies (black, n = 102) and TAZ À/À flies (gray, n = 74) at 1 week old (P = 0.318).…”

G-Protein signaling accelerates stem cell divisions in Drosophila males

“…5-HT and OA are commercially available and were previously successfully fed to adult animals to study changes in their behavior. In these experiments, 1-100mM of 5-HT and 30-70µM of OA evoked behavioral responses (Crocker and Sehgal, 2008;Majeed et al, 2014;Sujkowski et al, 2017;Willard et al, 2006). We did observed these behavioral responses when animals were fed these concentrations, but no increase in MI GSC was apparent.…”

A neural circuit arbitrates between perseverance and withdrawal in hungry Drosophila

“…This ventral cluster contains several types of OA neurons, some of which appear to receive information from ventral regions such as the SEZ and project axons to diverse higher brain regions, including the mushroom body (MB), in a cell type specific manner (Busch et al, 2009;Busch and Tanimoto, 2010). OA has been implicated in a number of behaviors including arousal, sleep, endurance, aggression, memory and energy and nutrient homeostasis (Corrales-Carvajal et al, 2016;Crocker et al, 2010;Schwaerzel et al, 2003;Sujkowski et al, 2017;Watanabe et al, 2017;Yang et al, 2015). Outside of the brain, octopaminergic signaling is necessary at the neuromuscular junction and promotes increased locomotion under food deprivation (Koon et al, 2011).…”