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

Author:

Aranda-Martínez Paula1ORCID,Fernández-Martínez José1ORCID,Ramírez-Casas Yolanda1ORCID,Rodríguez-Santana César1ORCID,Rusanova Iryna12ORCID,Escames Germaine12ORCID,Acuña-Castroviejo Darío123ORCID

Affiliation:

1. Centro de Investigación Biomédica, Facultad de Medicina, Departamento de Fisiología, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, Spain

2. Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Ibs.Granada, Hospital Universitario San Cecilio, 18016 Granada, Spain

3. UGC de Laboratorios Clínicos, Hospital Universitario San Cecilio, 18016 Granada, Spain

Abstract

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.

Funder

FEDER Andalucía

PAIDI 2020, Junta de Andalucía

ISCIII

Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía

PFIS fellowship

Publisher

MDPI AG

Subject

Cell Biology,Clinical Biochemistry,Molecular Biology,Biochemistry,Physiology

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