An Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster

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dc.catalogadorgjm
dc.contributor.authorZárate Canales, Rafaella Victoria
dc.contributor.authorHidalgo, Sergio
dc.contributor.authorNavarro, Nicole
dc.contributor.authorMolina Mateo, Daniela Francisca
dc.contributor.authorArancibia, Duxan
dc.contributor.authorRojo Cortés, Francisca Rayén
dc.contributor.authorOliva, Carlos
dc.contributor.authorAndrés Coke, María Estela
dc.contributor.authorZamorano, Pedro
dc.contributor.authorCampusano Astorga, Jorge Mauricio
dc.date.accessioned2023-01-04T13:09:59Z
dc.date.available2023-01-04T13:09:59Z
dc.date.issued2022
dc.description.abstractParkinson's disease (PD) is a neurodegenerative disease characterized by motor symptoms and dopaminergic cell loss. A pre-symptomatic phase characterized by non-motor symptoms precedes the onset of motor alterations. Two recent PET studies in human carriers of mutations associated with familial PD demonstrate an early serotonergic commitment-alteration in SERT binding-before any dopaminergic or motor dysfunction, that is, at putative PD pre-symptomatic stages. These findings support the hypothesis that early alterations in the serotonergic system could contribute to the progression of PD, an idea difficult to be tested in humans. Here, we study some components of the serotonergic system during the pre-symptomatic phase in a well-characterized Drosophila PD model, Pink1(B9) mutant flies. We detected lower brain serotonin content in Pink1(B9) flies, accompanied by reduced activity of SERT before the onset of motor dysfunctions. We also explored the consequences of a brief early manipulation of the serotonergic system in the development of motor symptoms later in aged animals. Feeding young Pink1(B9) flies with fluoxetine, a SERT blocker, prevents the loss of dopaminergic neurons and ameliorates motor impairment observed in aged mutant flies. Surprisingly, the same pharmacological manipulation in young control flies results in aged animals exhibiting a PD-like phenotype. Our findings support that an early dysfunction in the serotonergic system precedes and contributes to the onset of the Parkinsonian phenotype in Drosophila.
dc.fechaingreso.objetodigital2023-01-04
dc.fuente.origenWOS
dc.identifier.doi10.3390/cells11091544
dc.identifier.eissn2073-4409
dc.identifier.urihttps://doi.org/10.3390/cells11091544
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/66177
dc.identifier.wosidWOS:000795432500001
dc.information.autorucFacultad de ciencias biológicas ; Zárate Canales, Rafaella Victoria ; 0000-0001-7250-9007 ; 1031192
dc.information.autorucFacultad de ciencias biológicas ; Molina Mateo, Daniela Francisca ; S/I ; 205481
dc.information.autorucFacultad de ciencias biológicas ; Rojo Cortés, Francisca Rayén ; 0000-0003-2332-8423 ; 221031
dc.information.autorucFacultad de ciencias biológicas ; Andrés Coke, María Estela ; 0000-0002-2078-2770 ; 74858
dc.information.autorucFacultad de ciencias biológicas ; Campusano Astorga, Jorge Mauricio ; 0000-0001-5254-8340 ; 3965
dc.issue.numero9
dc.language.isoen
dc.nota.accesoContenido completo
dc.publisherMDPI
dc.rightsacceso abierto
dc.subjectParkinson's disease
dc.subjectDrosophila melanogaster
dc.subjectPINK1
dc.subjectPre-symptomatic phase
dc.subjectSerotonin
dc.subjectSERT
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleAn Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster
dc.typeartículo
dc.volumen11
sipa.codpersvinculados1031192
sipa.codpersvinculados205481
sipa.codpersvinculados221031
sipa.codpersvinculados74858
sipa.codpersvinculados3965
sipa.indexWOS
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