Browsing by Author "Rojo Cortés, Francisca Rayén"

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    An Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster
    (MDPI, 2022) Zárate Canales, Rafaella Victoria; Hidalgo, Sergio; Navarro, Nicole; Molina Mateo, Daniela Francisca; Arancibia, Duxan; Rojo Cortés, Francisca Rayén; Oliva, Carlos; Andrés Coke, María Estela; Zamorano, Pedro; Campusano Astorga, Jorge Mauricio
    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.
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    Functional characterization of Lipophorin Receptors in the mushroom body of Drosophila melanogaster
    (2022) Rojo Cortés, Francisca Rayén; Marzolo Canales, María Paz; Campusano Astorga, Jorge Mauricio; Pontificia Universidad Católica de Chile. Facultad de Ciencias Biológicas
    Los receptores de lipoforina de Drosophila melanogaster (LpRs), LpR1 y LpR2, median la captación de lípidos. Los ortólogos de estos receptores en vertebrados, ApoER2 y VLDL-R, se unen a Reelina, la que no está presente en las moscas. Estas proteínas están asociadas con el desarrollo y función del hipocampo y la corteza cerebral. Actualmente se desconoce si los LpRs desempeñan funciones similares en el cerebro de Drosophila. Informamos que las moscas deficientes en LpRs exhiben una memoria olfativa y patrones de sueño alterados, los que parecen reflejar los defectos anatómicos encontrados en un área de asociación cerebral crítica, el cuerpo fungiforme (MB). Además, las neuronas del MB respondieron a Reelina aumentando su árbol neurítico. Este efecto depende de LpRs y Dab, el ortólogo en Drosophila de la proteína adaptadora del la señalización de Reelina Dab1. In vitro, dos isoformas largas de LpRs permitieron la internalización de Reelina. Además, se estudió la proteína no caracterizada anteriormente, la que dada su similitud con F-spondina y Reelina llamaremos Drospondina, como un posible ligando endógeno para los LpRs. Drospondina es expresada por una población de glía a lo largo del desarrollo. Dado que se encontró Drospondina rodeando los lóbulos del MB, estudiamos el MB de moscas deficientes para Drospondin, encontrándose defectos en su desarrollo. Además, la falta de Drospondina alteró la homeostasis del sueño. También encontramos que Drospondina interactúa genéticamente con los LpRs. Estos hallazgos demuestran que LpRs, Dab y Drospondina contribuyen al desarrollo y la función de MB, lo que respalda la existencia de señalización dependiente de estas proteínas en Drosophila.
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    Lipophorin receptors regulate mushroom body development and complex behaviors in Drosophila
    (2022) Rojo Cortés, Francisca Rayén; Fuenzalida-Uribe, Nicolás; Tapia Valladares, Victoria; Roa, Candy B.; Hidalgo Sotelo, Sergio Ignacio; González Ramírez, María Constanza; Oliva Olave, Carlos Andrés; Campusano Astorga, Jorge Mauricio; Marzolo Canales, María Paz
    Background: Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain. Results: We report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the mushroom bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurite arborization. This effect depends on LpRs and Dab, the Drosophila ortholog of the Reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events. Conclusions: These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.