Browsing by Author "Gregorio, Cristian de"
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Item Collateral Sprouting of Peripheral Sensory Neurons Exhibits a Unique Transcriptomic Profile(2020) Lemaitre, Dominique; Llavero Hurtado, Maica; Gregorio, Cristian de; Oñate, Maritza; Martínez, Gabriela; Catenaccio, Alejandra; Wishart, Thomas M.; Court, Felipe A.Peripheral nerve injuries result in motor and sensory dysfunction which can be recovered by compensatory or regenerative processes. In situations where axonal regeneration of injured neurons is hampered, compensation by collateral sprouting from uninjured neurons contributes to target reinnervation and functional recovery. Interestingly, this process of collateral sprouting from uninjured neurons has been associated with the activation of growth-associated programs triggered by Wallerian degeneration. Nevertheless, the molecular alterations at the transcriptomic level associated with these compensatory growth mechanisms remain to be fully elucidated. We generated a surgical model of partial sciatic nerve injury in mice to mechanistically study degenerationinduced collateral sprouting from spared fibers in the peripheral nervous system. Using next-generation sequencing and Ingenuity Pathway Analysis, we described the sprouting-associated transcriptome of uninjured sensory neurons and compare it with the activated by regenerating neurons. In vitro approaches were used to functionally assess sprouting gene candidates in the mechanisms of axonal growth. Using a novel animal model, we provide the first description of the sprouting transcriptome observed in uninjured sensory neurons after nerve injury. This collateral sprouting-associated transcriptome differs from that seen in regenerating neurons, suggesting a molecular program distinct from axonal growth. We further demonstrate that genetic upregulation of novel sproutingassociated genes activates a specific growth program in vitro, leading to increased neuronal branching. These results contribute to our understanding of the molecular mechanisms associated with collateral sprouting in vivo. The data provided here will therefore be instrumental in developing therapeutic strategies aimed at promoting functional recovery after injury to the nervous system.Publication Gut Microbiota-Derived Extracellular Vesicles Influence Alcohol Intake Preferences in Rats(2025) Díaz-Ubilla, Macarena; Figueroa-Valdés, Aliosha I.; Tobar, Hugo E.; Quintanilla, María Elena; Díaz, Eugenio; Morales, Paola; Berríos-Cárcamo, Pablo; Santapau, Daniela; Gallardo, Javiera; Gregorio, Cristian de; Ugalde, Juan; Rojas, Carolina; Gonzalez-Madrid, Antonia; Ezquer, Marcelo; Israel, Yedy; Alcayaga-Miranda, Francisca; Ezquer, FernandoGrowing preclinical and clinical evidence suggests a link between gutmicrobiota dysbiosis and problematic alcohol consumption. Extracellular vesicles (EVs) are key mediators involved in bacteria-to-host communication. However, their potential role in mediating addictive behaviour remains unexplored. This study investigates the role of gut microbiota-derived bacterial extracellular vesicles (bEVs) in driving high alcohol consumption. bEVs were isolated from the gut microbiota of a high alcoholdrinking rat strain (UChB rats), either ethanol-naïve or following chronic alcohol consumption and administered intraperitoneally or orally to alcohol-rejecting male and femaleWistar rats. Both types of UChB-derived bEVs increased Wistar’s voluntary alcohol consumption (three bottle choice test) up to 10-fold (p < 0.0001), indicating that bEVs are able and sufficient to transmit drinking behaviour across different rat strains. Molecular analysis revealed that bEVs administration did not induce systemic or brain inflammation in the recipient animals, suggesting that the increased alcohol intake triggered by UChB-derived bEVs operates through an inflammation-independent mechanism. Furthermore,we demonstrate that the vagus nerve mediates the bEV-induced increase in alcohol consumption, as bilateral vagotomy completely abolished the high drinking behaviour induced by both intraperitoneally injected and orally administered bEVs. Thus, this study identifies bEVs as a novel mechanism underlying gut microbiota-induced high alcohol intake in a vagus nerve-dependent manner.