Article Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
Metadatos
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Aranda Martínez, Paula; Fernández Martínez, José; Ramírez Casas, Yolanda; Rodríguez Santana, César; Rusanova Rusanova, Iryna; Escames Rosa, Germaine; Acuña Castroviejo, DaríoEditorial
MDPI
Materia
Zebrafish Parkinson's disease Clock genes Chronodisruption Melatonin
Fecha
2023-04-18Referencia bibliográfica
Aranda-Martínez, P.; Fernández-Martínez, J.; Ramírez-Casas, Y.; Rodríguez-Santana, C.; Rusanova, I.; Escames, G.; Acuña-Castroviejo, D. Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment. Antioxidants 2023, 12, 954. [https://doi.org/10.3390/antiox12040954]
Patrocinador
A-CTS.205.UGR18 from the Projects I+D+i Programa Operativo FEDER Andalucía 2014–2020; P18-RT-698 from PAIDI 2020, Junta de Andalucía; CB16-10-00238 (ISCIII); European Regional Development Fund/European Social Fund) “Investing in your future”); Consejería de Innovación, Ciencia y Empresa; Junta de Andalucía (CTS-101), Spain; FPU fellowships from the Ministerio de Educación, Spain; PFIS fellowship from the grant no. PI19-01372 (FIS, ISCIII; Fellowship from the grant no. P18-RT-698; Garantía Juvenil, Fondo Social EuropeoResumen
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 M 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 M.
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.