Cardiac performance in a familial Parkinson´s disease model

SANTALLA MANUELA; GOMEZ IVANA; DEL VALLE SOFIA; CIOCCI PARDO ALEJANDRO; VALVERDE CARLOS A; FERRERO PAOLA

virtual

Congreso; SAFIS ALACF 2021 join meeting; 2021

SAFIS

Introduction: Mutations in PARK7, which encodes DJ-1 protein, are associated with familial Parkinson´s disease (FPD). DJ-1 plays a key role in the maintenance of redox state and mitochondrial performance in cardiac tissue. Loss of DJ-1 function induced by mutations involved in FPD might affect cardiac performance. Objective: The objective was to investigate if the systemic deletion of the DJ-1β gene (Park flies), the Drosophila ortholog of human DJ-1, affects the cardiac function in a Drosophila melanogaster genetic model of FPD. Methods: Park flies and wild-type flies were studied at 7 and 40 days after emerging from the puparium. Locomotor activity was evaluated by climbing assays. Cardiac performance was studied in semi-intact heart preparations tracking the movement of the heart by microscopy. Mitochondrial membrane potential was assessed using Rodamine-123 assay. Results: 7-day-old Park flies showed a reduced climbing ability consisted with a PD phenotype. Compared to control, young Park flies exhibited reduced heart rate (HR: beats/min) 136,1 ± 13,48 n=14 vs 100,2 ± 6,75 n=17; and contractility (µM) (23,19 ± 2,7 N=11 vs 15,31 ± 1,33 N=15). Diastolic interval (sec) was augmented (0,4 ± 0,04 N=14 vs 0,56 ± 0,04 N=17). Forty-day-old flies showed an accentuated reduction of HR (105 ± 9,03 N=12 vs 80,35 ± 6,7 N=15), a lengthening rate (µM/sec) of contraction (0.48 ± 0.07 N=9 vs 0.3 ± 0.04 N=15) and relaxation (0.47 ± 0.06 N=9 vs 0.25 ± 0.03 N=15). Park flies did not expressed changes in the mitochondrial state at 7 or 40 days. Data are mean ± SE. P-values were determined using Student´s test. Conclusion: Our results show that systemic deletion of DJ-1β impairs the cardiac performance without changes in the mitochondrial state. These effects were observed in young flies, even before a motor impairment had been manifested, indicating that cardiac effects precede motor impairment.