Artículo
Plasma membrane calcium ATPase downregulation in dopaminergic neurons alters cellular physiology and motor behaviour in Drosophila melanogaster
Erhardt, Brenda
; Marcora, Maria Silvina
; Frenkel, Lia
; Bochicchio, Pablo Alejandro
; Bodin, Diego Hernán; Silva, Berenice Anabel; Farias, Maria Isabel
; Allo, Miguel Angel; Höcht, Christian; Ferrari, Carina Cintia
; Pitossi, Fernando Juan
; Leal, Maria Celeste
Fecha de publicación:
09/2021
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
European Journal of Neuroscience
ISSN:
0953-816X
e-ISSN:
1460-9568
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The accumulation of Ca2+ 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 Ca2+ increment in dopaminergic neurons physiology, we downregulated the plasma membrane Ca2+ ATPase (PMCA), a pump that extrudes cytosolic Ca2+, by expressing PMCARNAi in Drosophila melanogaster dopaminergic neurons. In these animals, we observed major locomotor alterations paralleled to higher cytosolic Ca2+ 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 Ca2+ that lead to augmented oxidative stress in a dopaminergic environment, added to a rise in synaptic vesicles and dopamine levels.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos (IMTIB)
Articulos de INSTITUTO DE MEDICINA TRASLACIONAL E INGENIERIA BIOMEDICA
Articulos de INSTITUTO DE MEDICINA TRASLACIONAL E INGENIERIA BIOMEDICA
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
Erhardt, Brenda; Marcora, Maria Silvina; Frenkel, Lia; Bochicchio, Pablo Alejandro; Bodin, Diego Hernán; et al.; Plasma membrane calcium ATPase downregulation in dopaminergic neurons alters cellular physiology and motor behaviour in Drosophila melanogaster; Wiley Blackwell Publishing, Inc; European Journal of Neuroscience; 54; 6; 9-2021; 5915-5931
Compartir
Altmétricas