PUBLICATION
In Vivo Determination of Mitochondrial Respiration in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Zebrafish Reveals the Efficacy of Melatonin in Restoring Mitochondrial Normalcy
- Authors
- Díaz-Casado, M.E., Rusanova, I., Aranda, P., Fernández-Ortiz, M., Sayed, R.K.A., Fernández-Gil, B.I., Hidalgo-Gutiérrez, A., Escames, G., López, L.C., Acuña-Castroviejo, D.
- ID
- ZDB-PUB-171204-22
- Date
- 2017
- Source
- Zebrafish 15(1): 15-26 (Journal)
- Registered Authors
- Keywords
- ETS capacity, in vivo respiration, melatonin, proton leak, zebrafish embryos
- MeSH Terms
-
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects*
- Animals
- Embryo, Nonmammalian/drug effects*
- Embryo, Nonmammalian/metabolism
- Embryo, Nonmammalian/pathology
- Energy Metabolism*
- MPTP Poisoning/drug therapy*
- MPTP Poisoning/metabolism
- MPTP Poisoning/pathology
- Melatonin/pharmacology*
- Mitochondria/drug effects
- Mitochondria/pathology
- Mitochondria/physiology*
- Neurotoxins/toxicity
- Oxidative Stress/drug effects
- Protective Agents/pharmacology
- Zebrafish/embryology
- Zebrafish/physiology*
- PubMed
- 29185873 Full text @ Zebrafish
Citation
Díaz-Casado, M.E., Rusanova, I., Aranda, P., Fernández-Ortiz, M., Sayed, R.K.A., Fernández-Gil, B.I., Hidalgo-Gutiérrez, A., Escames, G., López, L.C., Acuña-Castroviejo, D. (2017) In Vivo Determination of Mitochondrial Respiration in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Zebrafish Reveals the Efficacy of Melatonin in Restoring Mitochondrial Normalcy. Zebrafish. 15(1):15-26.
Abstract
Although mitochondria dysfunction is related to multiple diseases, no in vivo studies are available on mitochondrial respiration in animal parkinsonian models. Our aim is to analyze in vivo mitochondrial respiration, which reflects changes in mitochondrial bioenergetics more precisely than in vitro mitochondrial preparations. These experiments can be carried out in zebrafish embryos, which were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) from 24 to 72 hours postfertilization (hpf). A reduction in electron transfer system capacity, ATP turnover, and increased proton leak were observed at 72 hpf in MPTP-treated embryos. These changes were followed by a significant oxidative stress due to inhibition in antioxidative defense and autophagy impairment. After removing MPTP from the treatment at 72 hpf, these bioenergetic deficiencies persisted up to 120 hpf. The administration of melatonin to zebrafish embryos at 72 hpf, when mitochondrial dysfunction is already present, restored the respiratory capacity and ATP production, reduced oxidative stress, and normalized autophagy after 48 h. Melatonin also counteracted mortality and embryonic malformations due to MPTP. Our results confirm for the first time the efficacy of melatonin in restoring parkinsonian phenotypes in animals.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping