Ectopic expression of the cation-chloride cotransporter KCC2 in blood exosomes as a biomarker for functional rehabilitation.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2025-02-05 eCollection Date: 2025-01-01 DOI:10.3389/fnmol.2025.1522571

L Caccialupi Da Prato, A Rezzag Lebza, A Consumi, M Tessier, A Srinivasan, C Rivera, J Laurin, C Pellegrino

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引用次数: 0

Abstract

Background: Traumatic 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.

Methods: Using 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.

Results: After 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.

Conclusion: We 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.

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.