“Plasma Membrane Calcium Atpase downregulation in dopaminergic neurons alters cellular physiology and behavior in Drosophila melanogaster”

Abstract

Accumulation of calcium is proposed to account for selective dopaminergic neuron (DN) dysfunctionality, a characteristic of Parkinson´s 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>PMCA RNAi , PMCA was selectively reduced, leading to increased cytosolic calcium and mitochondrial oxidative stress with no neurodegeneration. In the eye, PMCA RNAi 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 nonmotor 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.