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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1522571
This article is part of the Research Topic SLC12A5-Dependent Neurological Disorders View all 5 articles

Ectopic Expression of Cation Chloride Cotransporters KCC2 in blood exosomes, used as a biomarker of functional rehabilitation

Provisionally accepted
Laura Caccialupi Da Prato Laura Caccialupi Da Prato 1Amina Rezzag Lebza Amina Rezzag Lebza 1Amandine Consumi Amandine Consumi 1Marine Tessier Marine Tessier 1Asha Srinivasan Asha Srinivasan 2Jérôme Laurin Jérôme Laurin 3Claudio Rivera Claudio Rivera 4Christophe Pellegrino Christophe Pellegrino 3*
  • 1 INSERM U901 Institut de Neurobiologie de la Méditerranée, Marseille, Provence-Alpes-Côte d'Azur, France
  • 2 JSS Academy of Higher Education and Research, Mysore, Karnataka, India
  • 3 Faculté des Sciences, Aix Marseille Université, Marseille, France
  • 4 Neuroscience Center, University of Helsinki, Helsinki, Uusimaa, Finland

The final, formatted version of the article will be published soon.

    Background. Traumatic brain injury (TBI) is the major cause of disabilities in the industrialized countries. Cognitive decline appears in the chronic phase of the pathology consecutively to cellular and molecular processes. Here we described the use of KCC2, a neuronal-specific potassium-chloride transporter as a potent biomarker to predict cognitive dysfunctions after TBI.Methods. Using neuronal and total exosomes collection from blood serum in controls and TBI subjects we were able to anticipate the decline of cognitive performance.Results. After TBI, we observed a significative and persistent loss of KCC2 expression in blood exosomes that is correlated to changes in network activity and cellular processes such as secondary neurogenesis. Furthermore, we have established a correlation between this decrease in KCC2 expression and the long-term consequences of brain trauma as well as identified a link between the loss of KCC2 expression and the emergence of depressive-like behavior observed in mice.We successfully validated our previous discoveries supporting the potential therapeutic benefits of bumetanide in mitigating post-traumatic depression following TBI. This effect is correlated with the recovery of KCC2 expression in blood exosomes and preventing extensive neuronal loss among interneurons as well as changes secondary neurogenesis.

    Keywords: biomarker, Traumatic Brain Injury, chloride homeostasis, KCC2 = potassium chloride cotransporter 2, exosome

    Received: 04 Nov 2024; Accepted: 20 Jan 2025.

    Copyright: © 2025 Caccialupi Da Prato, Lebza, Consumi, Tessier, Srinivasan, Laurin, Rivera and Pellegrino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Christophe Pellegrino, Faculté des Sciences, Aix Marseille Université, Marseille, France

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.