Browsing by Autor "Alejandro Luarte"

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A novel brain-to-gut communication pathway mediated by astrocyte-derived small extracellular vesicles modulates stress-induced intestinal inflammation.
(2024) Úrsula Wyneken; Liliana Yantén-Fuentes; Matías Pizarro; Carolina Rojas; Carolina Pradenas; Katherine Corvalán; Gonzalo Bustos; Alejandro Luarte; Federico Batiz; Patricia Luz‐Crawford
<title>Abstract</title> The connection between stress-induced mood disorders and inflammatory bowel diseases has long been acknowledged. Here, we hypothesize that psychological stress may regulate intestinal inflammation under stress conditions through the release of small extracellular vesicles derived from astrocytes (AsEVs). Sprague-Dawley rats were stressed by movement restriction. In-utero electroporation was performed to express a recombinant protein (BAP-TM) in astrocytes that is exported in AsEVs. AsEVs were also obtained from primary astrocyte cultures that were stimulated with DMSO or corticosterone (to emulate a stress condition). The inflammatory status in the blood and intestine was assessed by flow cytometry and histology, respectively. We found that recombinant AsEV proteins expressed in brain astrocytes as well as AsEVs harvested from primary astrocyte cultures contain the gut homing receptor CCR9 and target the small intestine in rats. At the histological level, inflammatory parameters (such as lymph vessel diameter or cell number in them) induced by movement restriction are restored to normal levels by treatment with AsEVs derived from primary astrocytes. On the contrary, AsEVs derived from corticosterone-treated astrocytes increase stress-induced intestinal inflammation. Furthermore, AsEVs can modulate the immune balance of the GALT: while AsEVs derived from control astrocyte cultures favor an anti-inflammatory profile (i.e., increased Treg/Th17 ratio), AsEVs derived from corticosterone-treated astrocytes have an opposite action. We here reveal an entirely new brain-to-gut AsEVs-mediated communication pathway that may impact on stress-induced inflammatory bowel pathophysiology. This research paves the way for novel, cutting-edge therapeutic approaches to tackle the complex interplay between stress and intestinal inflammatory diseases.
Author Reply to Peer Reviews of Local synthesis of Reticulon-1C lessens the outgrowth of injured axons and Spastin activity
(2025) Alejandro Luarte; Javiera Gallardo; Daniela Corvalán; Ankush Chakraborty; Cláudio Gouveia-Roque; Francisca Bertin; C. Contreras; Julio A. Ramírez; A Weber; Waldo Acevedo
Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons
(2026) Alejandro Luarte; Javiera Andrea Ojeda Gallardo; Daniela Corvalán; Ankush Chakraborty; Cláudio Gouveia Roque; Francisca Bertin; C. Contreras; Juan Pablo Ramírez; André Alberto Weber; Waldo Acevedo
The regenerative potential of developing cortical axons depends on intrinsic mechanisms, such as axon-autonomous protein synthesis, that are still not fully understood. An emerging factor in this regenerative response is the bidirectional interplay between microtubule dynamics and the axonal ER. We hypothesize that locally synthesized ER proteins regulate microtubule dynamics and the regeneration of cortical axons. RNA data mining identified the ER-shaping protein Reticulon-1 as a relevant candidate across eight axonal transcriptomes. Using microfluidics, we show that axonal treatment with a small RNA against Reticulon-1 mRNA (Reticulon-1 knockdown) increases outgrowth of injured cortical axons while reducing their tubulin levels. We show by live-cell imaging that axonal Reticulon-1 knockdown increases microtubule growth rate in noninjured axons and restores this parameter after injury. Axonal inhibition of the microtubule-severing protein Spastin prevents the effects of Reticulon-1 knockdown over tubulin levels and outgrowth. We provide evidence that the Reticulon-1C isoform is synthesized within axons and attenuates Spastin-mediated microtubule severing. These findings support a model in which axonal protein synthesis regulates microtubule dynamics and axon outgrowth after injury.