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Plasma membrane calcium ATPase downregulation in dopaminergic neurons alters cellular physiology and motor behaviour in Drosophila melanogaster
Author(s) -
Erhardt Brenda,
Marcora María Silvina,
Frenkel Lía,
Bochicchio Pablo Alejandro,
Bodin Diego Hernán,
Silva Berenice Anabel,
Farías María Isabel,
Allo Miguel Ángel,
Höcht Christian,
Ferrari Carina Cintia,
Pitossi Fernando Juan,
Leal María Celeste
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15401
Subject(s) - dopaminergic , plasma membrane ca2+ atpase , dopamine , drosophila melanogaster , biology , microbiology and biotechnology , oxidative stress , synaptic vesicle , neuroscience , mitochondrion , atpase , endocrinology , vesicle , biochemistry , enzyme , membrane , gene
The accumulation of Ca 2+ and its subsequent increase in oxidative stress is proposed to be involved in selective dysfunctionality of dopaminergic neurons, the main cell type affected in Parkinson's disease. To test the in vivo impact of Ca 2+ increment in dopaminergic neurons physiology, we downregulated the plasma membrane Ca 2+ ATPase (PMCA), a pump that extrudes cytosolic Ca 2+ , by expressing PMCA RNAi in Drosophila melanogaster dopaminergic neurons. In these animals, we observed major locomotor alterations paralleled to higher cytosolic Ca 2+ and increased levels of oxidative stress in mitochondria. Interestingly, although no overt degeneration of dopaminergic neurons was observed, evidences of neuronal dysfunctionality were detected such as increases in presynaptic vesicles in dopaminergic neurons and in the levels of dopamine in the brain, as well as presence of toxic effects when PMCA was downregulated in the eye. Moreover, reduced PMCA levels were found in a Drosophila model of Parkinson's disease, Parkin knock‐out, expanding the functional relevance of PMCA reduction to other Parkinson's disease‐related models. In all, we have generated a new model to study motor abnormalities caused by increments in Ca 2+ that lead to augmented oxidative stress in a dopaminergic environment, added to a rise in synaptic vesicles and dopamine levels.

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