期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 54, 期 6, 页码 5915-5931出版社
WILEY
DOI: 10.1111/ejn.15401
关键词
calcium; dopaminergic neurons; Drosophila melanogaster; Parkin; Parkinson's disease; plasma membrane Ca(2+)ATPase
资金
- Foundation Baron fellowship [PICT3336-ANPCyT, PIP485-CONICET]
- ISN-CAEN 2015
The study showed that the accumulation of Ca2+ in dopaminergic neurons could lead to motor abnormalities and increased oxidative stress levels. Although no significant degeneration of neurons was observed, evidence of neuronal dysfunctionality was detected, indicating the functional relevance of Ca2+ increase in Parkinson's disease-related models.
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 PMCA(RNAi) 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据