Browsing by Author "Campusano Astorga, Jorge Mauricio"

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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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    Characterization of a presymptomatic stage in a Drosophila Parkinson's disease model: Unveiling dopaminergic compensatory mechanisms
    (2017) Molina-Mateo, Daniela; Fuenzalida Uribe, Nicolás Leonardo; Hidalgo, Sergio; Molina-Fernández, Claudia; Abarca, Jorge; Zárate Canales, Rafaella Victoria; Escandón, Marcela; Figueroa, Reinaldo; Tevy, María Florencia; Campusano Astorga, Jorge Mauricio
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    Dopamine D1 and corticotrophin-releasing hormone type-2α receptors assemble into functionally interacting complexes in living cells
    (2014) Fuenzalida, J.; Galaz, P.; Araya, K.; Slater Guzmán, Paula Gabriela; Blanco Nahuelqueo, Elías; Campusano Astorga, Jorge Mauricio; Ciruela, F.; Gysling Caselli, Katia
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    Dysbiosis prevents age-dependent phenotypes in drosphila Pink1B9 a fly model for parkinson's disease
    (2022) Molina Mateo, Daniela Francisca; Campusano Astorga, Jorge Mauricio; Pontificia Universidad Católica de Chile. Facultad de Medicina
    La interacción entre el sistema nervioso entérico (SNE) y el sistema nervioso central (SNC), comúnmente conocido como el eje Intestino-Cerebro, consiste en una comunicación bidireccional regulada a nivel endocrino, inmunológico y neuronal, el desequilibrio en su normal funcionamiento se ha asociado recientemente con varios trastornos neuropsiquiátricos y neurodegenerativos. La investigación sobre este eje podría ofrecernos nuevos blancos terapéuticos para una amplia gama de enfermedades, incluida la enfermedad de Parkinson (EP). La EP es un desorden neurodegenerativo caracterizado por alteraciones motoras, las cuales son precedidas por lo que se denomina una etapa prodrómica o premotora donde es posible observar síntomas no motores. En esta tesis se propone manipular la microbiota intestinal en etapas premotoras tempranas de un modelo de EP en mosca generado por una deleción en el gen Pink1 (Pink1B9), para evaluar si esta manipulación podría afectar la progresión temporal de los síntomas de la EP. En este trabajo, se analizó si existían diferencias en la composición de la microbiota del intestino medio a los 8-9 días posteriores a la eclosión y se generó un modelo de disbiosis (desequilibrio microbiano) intestinal en Drosophila mediante un tratamiento crónico con antibiótico (kanamicina, 0,5 mM), durante un máximo de 16 días. Finalmente, mediante el uso de un sistema de registro, evaluamos individualmente en moscas macho diversos parámetros de comportamiento motores y no motores en las moscas tratadas y no tratadas con kanamicina. Los resultados obtenidos en esta tesis evidencian una diferencia sustancial en la composición de la microbiota intestinal del mutante Pink1B9 en comparación con las moscas control. Los datos también muestran que el tratamiento con kanamicina induce la recuperación de algunos de los parámetros no motores en etapa premotora estudiados en la EP, mientras que no hay cambios en los parámetros locomotores en la etapa. Por otro lado, el tratamiento específicamente durante la etapa premotora tiene un efecto prolongado induciendo una mejora en la capacidad locomotora de las moscas de control y mutantes.
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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.
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    Modeling of the binding of octopamine and dopamine in insect monoamine transporters reveals structural and electrostatic differences
    (2019) Arancibia, S.; Marambio, M.; Campusano Astorga, Jorge Mauricio; Fierro Huerta, Angélica
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    Muscarinic ACh receptors contribute to aversive olfactory learning in drosophila
    (2015) Silva, Bryon; Molina Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano Astorga, Jorge Mauricio
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    nAChR-induced octopamine release mediates the effect of nicotine on a startle response in Drosophila melanogaster
    (2013) Fuenzalida Uribe, Nicolás Leonardo; Meza Cárdenas, Rodrigo Alexis; Hoffmann, Hernán A.; Varas Orozco, Rodrigo; Campusano Astorga, Jorge Mauricio
    Biogenic amines (BAs) play a central role in the generation of complex behaviors in vertebrates and invertebrates, including the fly Drosophila melanogaster. The comparative advantages of Drosophila as a genetic model to study the contribution of BAs to behaviors stumble upon the difficulty to access the fly brain to ask relevant physiological questions. For instance, it is not known whether the activation of nicotinic acetylcholine receptors (nAChRs) induces the release of BAs in fly brain, a phenomenon associated to several behaviors in vertebrates. Here, we describe a new preparation to study the efflux of BAs in the adult fly brain by in vitro chronoamperometry. Using this preparation we show that nAChR agonists including nicotine induce a fast, transient, dose-dependent efflux of endogenous BAs, an effect mediated by -bungarotoxin-sensitive nAChRs. By using different genetic tools we demonstrate that the BA whose efflux is induced by nAChR activation is octopamine (Oct). Furthermore, we show that the impairment of a mechanically induced startle response after nicotine exposure is not observed in flies deficient in Oct transmission. Thus, our data show that the efflux of BAs in Drosophila brain is increased by nAChR activation as in vertebrates, and that then AChR-induced Oct release could have implications in a nicotine-induced behavioral response.
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    nAChR-mediated calcium responses and plasticity in Drosophila Kenyon cells
    (2007) Campusano Astorga, Jorge Mauricio
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    Octopamine and dopamine differentially modulate the nicotine-induced calcium response in drosophila mushroom body kenyon cells
    (2014) Goles Varela, Nicolás Ignacio; Fuenzalida Uribe, Nicolás Leonardo; Campusano Astorga, Jorge Mauricio
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    Parkinsonian phenotypes induced by Synphilin-1 expression are differentially contributed by serotonergic and dopaminergic circuits and suppressed by nicotine treatment
    (2023) Angel Carvajal-Oliveros; Efthimios M. C. Skoulakis; Carmen Dominguez-Baleón; Iván Sánchez-Díaz; Diego Zambrano-Tipan; René Hernández-Vargas; Campusano Astorga, Jorge Mauricio; Verónica Narváez-Padilla; Enrique Reynaud
    Synphilin-1 is a protein encoded by the human SNCAIP gene whose function has yet to be fully understood. However, it has been linked to familial Parkinson’s disease (PD). Synphilin-1 is a major component of the Lewy bodies found in neurons in the substantia nigra pars compacta of PD patients. Synphilin-1 expression in serotonergic and/or dopaminergic neurons of Drosophila melanogaster induces neurodegeneration, as well as motor and non-motor PD like symptoms. In this work, we examined the contribution of the serotonergic and dopaminergic circuits in the development of PD-like phenotypes. We found that olfactory and visual symptoms are majorly contributed by the serotonergic system, and that motor symptoms and reduction in survival are mainly contributed by the dopaminergic system. Chronic nicotine treatment was able to suppress several of these symptoms. These results indicate that both the serotonergic and dopaminergic systems contribute to different aspects of PD symptomatology and that nicotine has beneficial effects on specific symptoms.
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    Primary neuronal cultures from the brains of late stage Drosophila pupae
    (2007) Sicaeros, B.; Campusano Astorga, Jorge Mauricio
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    Serotonin Receptors Expressed in Drosophila Mushroom Bodies Differentially Modulate Larval Locomotion
    (2014) Silva Bustos, Bryon Arnaldo; Goles Varela, Nicolás Ignacio; Varas Orozco, Rodrigo; Campusano Astorga, Jorge Mauricio
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    Slit neuronal secretion coordinates optic lobe morphogenesis in Drosophila
    (2020) Caipo, L.; González Ramírez, María Constanza; Guzman-Palma, P.; Contreras, E.G.; Palominos, T.; Fuenzalida Uribe, Nicolás Leonardo; Hassan, B.A.; Campusano Astorga, Jorge Mauricio; Sierralta, J.; Oliva Olave, Carlos Andrés