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Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment

Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson’s disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of...

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Autores principales: Aranda-Martínez, Paula, Fernández-Martínez, José, Ramírez-Casas, Yolanda, Rodríguez-Santana, César, Rusanova, Iryna, Escames, Germaine, Acuña-Castroviejo, Darío
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136267/
https://www.ncbi.nlm.nih.gov/pubmed/37107331
http://dx.doi.org/10.3390/antiox12040954
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author Aranda-Martínez, Paula
Fernández-Martínez, José
Ramírez-Casas, Yolanda
Rodríguez-Santana, César
Rusanova, Iryna
Escames, Germaine
Acuña-Castroviejo, Darío
author_facet Aranda-Martínez, Paula
Fernández-Martínez, José
Ramírez-Casas, Yolanda
Rodríguez-Santana, César
Rusanova, Iryna
Escames, Germaine
Acuña-Castroviejo, Darío
author_sort Aranda-Martínez, Paula
collection PubMed
description Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson’s disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of this study was to evaluate the connection between clock genes and these rhythms in PD, and whether melatonin administration reestablished the normal clock function. Parkinsonism was induced with 600 μM MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in 24–120 h post fertilization (hpf) zebrafish embryos and melatonin was administered at a dose of 1 μM. Day–night melatonin rhythm disappeared in MPTP-treated embryos, which showed an advance in the activity phase in parallel with changes in the rhythm of clock genes. An alteration in the fission-to-fusion mitochondrial dynamics was also detected in parkinsonian embryos, increasing the former and leading to apoptosis. Melatonin administration to MPTP-treated embryos fully restored the circadian system, including the rhythms of clock genes, motor activity, melatonin rhythm, and mitochondrial dynamics, and decreasing apoptosis. Because clock-controlled rhythms such as sleep/wake alterations are early events in PD, the data here reported may point to chronodisruption as one initial pathophysiological event of the disease.
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spelling pubmed-101362672023-04-28 Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment Aranda-Martínez, Paula Fernández-Martínez, José Ramírez-Casas, Yolanda Rodríguez-Santana, César Rusanova, Iryna Escames, Germaine Acuña-Castroviejo, Darío Antioxidants (Basel) Article Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson’s disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of this study was to evaluate the connection between clock genes and these rhythms in PD, and whether melatonin administration reestablished the normal clock function. Parkinsonism was induced with 600 μM MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in 24–120 h post fertilization (hpf) zebrafish embryos and melatonin was administered at a dose of 1 μM. Day–night melatonin rhythm disappeared in MPTP-treated embryos, which showed an advance in the activity phase in parallel with changes in the rhythm of clock genes. An alteration in the fission-to-fusion mitochondrial dynamics was also detected in parkinsonian embryos, increasing the former and leading to apoptosis. Melatonin administration to MPTP-treated embryos fully restored the circadian system, including the rhythms of clock genes, motor activity, melatonin rhythm, and mitochondrial dynamics, and decreasing apoptosis. Because clock-controlled rhythms such as sleep/wake alterations are early events in PD, the data here reported may point to chronodisruption as one initial pathophysiological event of the disease. MDPI 2023-04-18 /pmc/articles/PMC10136267/ /pubmed/37107331 http://dx.doi.org/10.3390/antiox12040954 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aranda-Martínez, Paula
Fernández-Martínez, José
Ramírez-Casas, Yolanda
Rodríguez-Santana, César
Rusanova, Iryna
Escames, Germaine
Acuña-Castroviejo, Darío
Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title_full Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title_fullStr Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title_full_unstemmed Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title_short Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
title_sort chronodisruption and loss of melatonin rhythm, associated with alterations in daily motor activity and mitochondrial dynamics in parkinsonian zebrafish, are corrected by melatonin treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136267/
https://www.ncbi.nlm.nih.gov/pubmed/37107331
http://dx.doi.org/10.3390/antiox12040954
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