title: Early alterations of mitochondrial morphology in dopaminergic neurons from Parkinson's disease-like pathology and time-dependent neuroprotection with D2 receptor activation.
abstract: Neuroprotection, to prevent vulnerable cell populations from dying, is perhaps the main strategy for treating Parkinson's disease (PD). Yet in clinical practice, therapy is introduced after the disease is well established and many neurons have already disappeared, while experimentally, treatment is typically added at the same time that PD pathology is instigated. This study uses an already established Drosophila melanogaster model of PD to test for early markers of neurodegeneration and if those markers are reversible following neuroprotective treatment. Specifically, we treat primary neuronal cultures with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) and track neuritic, dopaminergic mitochondria over time, observing a fragmenting change in their morphology before cell death. We then add a neuroprotective treatment (quinpirole, a D2 receptor agonist) at different timepoints to determine if the changes in mitochondrial morphology are reversible. We find that neuroprotective treatment must be added concomitantly to prevent changes in mitochondrial morphology and subsequent cell death. This work further supports Drosophila's use as a model organism and mitochondria's use as a biomarker for neurodegenerative disease. But mainly, this work highlights an import factor for experiments in neuroprotection - time of treatment. Our results highlight the problem that current neuroprotective treatments for PD may not be used the same way that they are tested experimentally.
authors.affiliation: Uppsala University, Department of Neuroscience, Functional Pharmacology, Biomedicinska Centrum, Husargatan 3, Box 593, 75124 Uppsala, Sweden. Electronic address: lyle.wiemerslage@neuro.uu.se.
authors.forename: Lyle
authors.initials: L
authors.lastname: Wiemerslage
authors.affiliation: Ohio University, Neuroscience Program, Department of Biological Sciences, Athens, OH 45701, United States.
authors.forename: Sazan
authors.initials: S
authors.lastname: Ismael
authors.affiliation: Ohio University, Neuroscience Program, Department of Biological Sciences, Athens, OH 45701, United States.
authors.forename: Daewoo
authors.initials: D
authors.lastname: Lee
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000473:pathology*; D004331:Drosophila melanogaster; D008928:Mitochondria / Q000473:pathology*; D000066829:Neuroprotection; D010300:Parkinson Disease / Q000473:pathology*; D019257:Quinpirole / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists*
chemical_list: D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015655:1-Methyl-4-phenylpyridinium
keywords: Cell culture; Dopamine; Drosophila; Mitochondria; Morphology; Parkinson