Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation
BackgroundTraumatic brain injury (TBI) is a major cause of disabilities in industrialized countries. Cognitive decline typically occurs in the chronic phase of the condition, following cellular and molecular processes. In this study, we described the use of KCC2, a neuronal-specific potassium–chlori...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2025.1522571/full |
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| author | L. Caccialupi Da Prato A. Rezzag Lebza A. Consumi M. Tessier A. Srinivasan C. Rivera C. Rivera J. Laurin C. Pellegrino |
| author_facet | L. Caccialupi Da Prato A. Rezzag Lebza A. Consumi M. Tessier A. Srinivasan C. Rivera C. Rivera J. Laurin C. Pellegrino |
| author_sort | L. Caccialupi Da Prato |
| collection | DOAJ |
| description | BackgroundTraumatic brain injury (TBI) is a major cause of disabilities in industrialized countries. Cognitive decline typically occurs in the chronic phase of the condition, following cellular and molecular processes. In this study, we described the use of KCC2, a neuronal-specific potassium–chloride cotransporter, as a potent biomarker to predict cognitive dysfunction after TBI.MethodsUsing neuronal and total exosome collections from the blood serum of the controls and patients with TBI, we were able to anticipate the decline in cognitive performance.ResultsAfter TBI, we observed a significant and persistent loss of KCC2 expression in the blood exosomes, which was correlated with the changes in the network activity and cellular processes such as secondary neurogenesis. Furthermore, we established a correlation between this decrease in KCC2 expression and the long-term consequences of brain trauma and identified a link between the loss of KCC2 expression and the emergence of depressive-like behavior observed in the mice.ConclusionWe successfully validated our previous findings, supporting the potential therapeutic benefits of bumetanide in mitigating post-traumatic depression (PTD) following TBI. This effect was correlated with the recovery of KCC2 expression in the blood exosomes, the prevention of extensive neuronal loss among the interneurons, and changes in secondary neurogenesis. |
| format | Article |
| id | doaj-art-f4d76786764a46b3ad5d5bdc44bf4bc4 |
| institution | Kabale University |
| issn | 1662-5099 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj-art-f4d76786764a46b3ad5d5bdc44bf4bc42025-02-05T07:32:23ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992025-02-011810.3389/fnmol.2025.15225711522571Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitationL. Caccialupi Da Prato0A. Rezzag Lebza1A. Consumi2M. Tessier3A. Srinivasan4C. Rivera5C. Rivera6J. Laurin7C. Pellegrino8Inmed, INSERM, Aix-Marseille University, Marseille, FranceInmed, INSERM, Aix-Marseille University, Marseille, FranceInmed, INSERM, Aix-Marseille University, Marseille, FranceInmed, INSERM, Aix-Marseille University, Marseille, FranceDivision of Nanoscience and Technology, School of Life Sciences, Center of Excellence in Molecular Biology and Regenerative Medicine, JSS Academy of Higher Education and Research, Mysore, IndiaInmed, INSERM, Aix-Marseille University, Marseille, FranceNeuroscience Center, University of Helsinki, Helsinki, FinlandInmed, INSERM, Aix-Marseille University, Marseille, FranceInmed, INSERM, Aix-Marseille University, Marseille, FranceBackgroundTraumatic brain injury (TBI) is a major cause of disabilities in industrialized countries. Cognitive decline typically occurs in the chronic phase of the condition, following cellular and molecular processes. In this study, we described the use of KCC2, a neuronal-specific potassium–chloride cotransporter, as a potent biomarker to predict cognitive dysfunction after TBI.MethodsUsing neuronal and total exosome collections from the blood serum of the controls and patients with TBI, we were able to anticipate the decline in cognitive performance.ResultsAfter TBI, we observed a significant and persistent loss of KCC2 expression in the blood exosomes, which was correlated with the changes in the network activity and cellular processes such as secondary neurogenesis. Furthermore, we established a correlation between this decrease in KCC2 expression and the long-term consequences of brain trauma and identified a link between the loss of KCC2 expression and the emergence of depressive-like behavior observed in the mice.ConclusionWe successfully validated our previous findings, supporting the potential therapeutic benefits of bumetanide in mitigating post-traumatic depression (PTD) following TBI. This effect was correlated with the recovery of KCC2 expression in the blood exosomes, the prevention of extensive neuronal loss among the interneurons, and changes in secondary neurogenesis.https://www.frontiersin.org/articles/10.3389/fnmol.2025.1522571/fullbiomarkertraumatic brain injurychloride homeostasispotassium chloride cotransporter 2 (KCC2)exosome |
| spellingShingle | L. Caccialupi Da Prato A. Rezzag Lebza A. Consumi M. Tessier A. Srinivasan C. Rivera C. Rivera J. Laurin C. Pellegrino Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation Frontiers in Molecular Neuroscience biomarker traumatic brain injury chloride homeostasis potassium chloride cotransporter 2 (KCC2) exosome |
| title | Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation |
| title_full | Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation |
| title_fullStr | Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation |
| title_full_unstemmed | Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation |
| title_short | Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation |
| title_sort | ectopic expression of the cation chloride cotransporter kcc2 in blood exosomes as a biomarker for functional rehabilitation |
| topic | biomarker traumatic brain injury chloride homeostasis potassium chloride cotransporter 2 (KCC2) exosome |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2025.1522571/full |
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