Dietary management and physical exercise can improve climbing defects and mitochondrial activity in Drosophila melanogaster parkin null mutants

Abstract

Physical exercise can improve gait, balance, tremor, flexibility, grip strength and motor coordination in Parkinson's disease (PD) patients. Several lines of evidence have also shown the therapeutic potential of dietary management and supplementation in halting the progression of PD. However, there is a lack of research on the combined effects of physical activity and nutrition in the progression of PD. We test the effects exercise and dietary modification in a Drosophila model of PD. In this study, we fed Drosophila parkin mutants high protein and high carbohydrate diets without and with stearic acid (4 treatments in total). In parallel, we subjected mutants to a regimen of exercise using a purpose-built 'Power tower' exercise machine. We then measured climbing ability, aconitase activity, and basal mitochondrial ROS levels. We observed that exercising parkin mutants fed the high protein diet improved their climbing ability and increased aconitase activity. There was an additional improvement in climbing and aconitase activity in exercised parkin mutants fed the high protein diet supplemented with stearic acid. No benefits of exercise were seen in parkin mutants fed the high carbohydrate diet. Combined, these results suggest that dietary management along with physical activty has potential to improve mitochondrial biogenesis and delay the progression of PD in Drosophila parkin mutants.

Keywords: Drosophila parkin mutants; carbohydrate; exercise; protein; stearic acid.

Figure 1.

Climbing index of yw males. Flies were exercised from day 3 until day 24, five days a week. The left side of the dashed line is the exercise period, and right side of the dashed line is the post-exercise period. A total of 90 exercised and 90 unexercised yw flies were used. Each treatment had 6 replicates with 15 flies per replicate. During week one they were exercised for 2 hours/session, during week two for 2.5 hours/session and during week three for 3 hours/session. The lines indicate the regression for exercise and unexercised flies (for exercised flies y = − 0.0094x + 0.95 and for unexercised flies y = − 0.0172x + 0.97). Symbols indicate mean, and bars indicate s.e.m.

Figure 2.

Optimization of exercise regimen for parkin- males using the climbing assay. Parkin- males had highest climbing index when exercised for 30 mins every alternate day (Regimen 4). Regimens 1, 2 and 3 exercised parkin- for 30, 60 and 120 mins every day, respectively. Regimens 4 and 5 exercised parkin- males for 30 and 60 mins, respectively on alternate days. Each regimen had 6 replicates of 12 parkin- males for 72 parkin- males/regimen (a total of 432 flies were included in the study). The flies were fed 1:2 P:C ratio diet throughout the exercise period. Bars indicate means and error bars indicate standard error. Significance determined by Dunnett’s test at *P < 0.05, **P < 0.01 (see text for details).

Figure 3.

Climbing index, aconitase activity and Basal ROS of unexercised and exercised parkin- males fed high Protein (1:2 P:C) and high Carbohydrate (1:16 P:C) ratio diet without (CTL) or with stearic acid (SA). A. Climbing. B. Mitochondrial aconitase activity. C Basal ROS. Bars indicate means and bars indicate s.e.m. Significance determined by Student’s t-test at *P < 0.05, **P < 0.01 and ***P < 0.001 (see text for details).