Plasma Membrane Calcium Atpase downregulation in dopaminergic neurons alters cellular physiology and behavior in Drosophila melanogaster
Erhardt, B.; Leal, M. C.; Marcora, M. S.; Frenkel, L.; Bochicchio, P. A.; Bodin, D. H.; Silva, B. A.; Farias, M. I.; Ferrari, C. C.; Allo, M. A.; Hocht, C.; Castano, E. M.; Pitossi, F. J.
Show abstract
Accumulation of calcium is proposed to account for selective dopaminergic neuron (DN) dysfunctionality, a characteristic of Parkinsons Disease (PD). To test the in vivo impact of calcium increment in DN physiology we downregulated the Plasma Membrane Calcium ATPase (PMCA), a bomb that extrudes cytosolic calcium, in those neurons in Drosophila melanogaster. Using th-GAL4>PMCARNAi, PMCA was selectively reduced, leading to increased cytosolic calcium and mitochondrial oxidative stress with no neurodegeneration. In the eye, PMCARNAi expression provoked a subtle disorganization, suggesting scarce toxicity. Interestingly, we observed several locomotor alterations and a higher level of dopamine in brains. Finally, flies presented a reduction of lifespan and a perimortem non-motor phenotype characterized by abdominal swelling, possibly due to constipation. We conclude that elevated cytosolic calcium in DN could trigger cellular dysfunction generating mitochondrial oxidative stress and motor and non-motor symptoms, typical of PD.
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