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

Cells

Duxan Arancibia¹  Pedro Zamorano¹  Jorge M. Campusano²  Nicole Navarro²  María Estela Andrés²  Daniela Molina-Mateo²  Rafaella V. Zárate²  Francisca Rojo-Cortés²  Carlos Oliva²  Sergio Hidalgo³ 

[1] Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1240000, Chile;Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile;Department of Entomology and Nematology, College of Agricultural and Environmental Sciences, University of California, Davis, CA 95616, USA;

关键词: Parkinson’s disease;    Drosophila melanogaster;    PINK1;    pre-symptomatic phase;    serotonin;    SERT;   

DOI  :  10.3390/cells11091544

来源: DOAJ

【 摘 要 】

Parkinson’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.

【 授权许可】

Unknown