Our understanding of the fundamental mechanisms that regulate neuronal activity remains incomplete. Among these, the balance of ions (such as chloride, sodium, potassium, and calcium) and water molecules at the cellular level plays a central role in information transmission within neural networks. Understanding these ion and water flows could provide valuable insight into the very earliest stages of neuronal dysfunction in certain diseases. However, these processes remain difficult to observe directly. Conventional methods, which are often invasive and limited to the study of isolated cells, do not allow for the simultaneous analysis of complex neural networks. To address this challenge, Antoine Godin and his team at Laval University are developing non-invasive optical tools capable of probing these mechanisms deep within the living brain.
Their research is based on a cutting-edge multimodal approach combining fluorescence microscopy, quantitative ion reporters, advanced image analysis, optogenetics, and mathematical modeling. This combination allows for the simultaneous study of ion concentrations, cell volume changes related to water flow, and the distribution of key proteins at the subcellular level. The team is particularly interested in ion cotransporters, proteins that regulate the movement of ions across the neuronal membrane and indirectly influence the excitatory or inhibitory nature of electrical signals.
By developing new experimental protocols and innovative imaging tools, the researchers have shown that chloride homeostasis is disrupted in several models of neurological diseases. They also observed that modulating the expression of certain cotransporters alleviated symptoms in animal models, while identifying similar signatures in humans.
These data suggest that ionic imbalances could serve as biomarkers for the diagnosis or monitoring of neurodegenerative diseases. By developing new optical imaging modalities capable of measuring these phenomena in intact tissue, Antoine Godin’s team is helping to lay the groundwork for quantification tools that enable earlier diagnosis and paves the way for innovative therapeutic strategies for brain diseases.
References
Keramidis, A., McAllister, B. B., Bourbonnais, J., Wang, F., Isabel, D., Rezaei, E., Sansonetti, R., Degagne, P., Hamel, J.-P., Nazari, M., Inayat, S., Dudley, J. C., Barbeau, A., Froux, L., Paquet, M.-E., Godin, A. G., Mohajerani, M. H., De Koninck, Y. (2023). Restoring neuronal chloride extrusion reverses cognitive decline linked to Alzheimer’s disease mutations, Brain, vol. 146, no. 12, pp. 4903–4915. https://doi.org/10.1093/brain/awad250
Khademullah, C. S., Bourbonnais, J., Chaineau, M. M., Castellanos-Montiel, M.-J., Keramidis, I., Legault, A., Paquet, M.-E., Abrahao, A., Zinman, L., Robertson, J., Durcan, T. M., Woodin, M. A., Godin, A. G., De Koninck, Y. (2023) KCC2 as a novel biomarker and therapeutic target for motor neuron degenerative disease, bioRxiv 2023.08.24.554410 https://doi.org/10.1101/2023.08.24.554410