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Using NMR spectroscopy to detect cell morphology alterations in vivo

Détecter les altérations de morphologie cellulaire par spectroscopie RMN in vivo

Julien Valette and his group at MIRCen have developed in vivo nuclear magnetic resonance spectroscopy techniques to quantify certain morphological characteristics of neurons and astrocytes. The team thereby seeks to contribute to a better understanding of the development of neurodegenerative diseases.

Published on 6 March 2019

​The brain is composed of not only neurons but also a number of support cells called glial cells collectively. One of these latter, the astrocyte, plays a critical role in neuron function. The morphology of astrocytes may change in specific ways, particularly over the course of neurodegenerative diseases. Thus, to better understand these cellular alterations and identify new biomarkers, a noninvasive imaging method permitting access to astrocyte morphology would be of great interest. However, the minuteness of these cells places them beyond the resolution of current in vivo imaging techniques.

Looking to circumvent this obstacle and within a project funded by the European Research Council (ERC), a team led by Julien Valette (IBFJ/MIRCen) has developed nuclear magnetic resonance (NMR) spectroscopy methods to quantify certain morphological characteristics of neurons and astrocytes in living research models. By measuring and modeling the diffusion of metabolites naturally present in the cells, the group was able to determine certain characteristics of the cellular structures confining that diffusion. As reported in the journal NeuroImage, their NMR spectroscopy approach enabled the detection of morphological alterations in a specific cell type. More precisely, in a murine model of astrocytic reactivity (which leads to astrocyte hypertrophy), the team showed that the in vivo diffusion properties of myo-inositol (a metabolite considered to be largely astrocyte-specific ) was specifically altered. The modeling of myo-inositol diffusion allowed the team to quantitatively determine astrocyte morphological variations, thereafter validated using confocal microscopy.

In their study, the researchers also observed—unexpectedly—major variations in lactate diffusion. That metabolite surely plays a fundamental role in a large number of brain processes, but its compartmentalization in different cell types remains controversial. However, the team's diffusion measurements suggested that lactate resides essentially in astrocytes in normal conditions but in neurons in the setting of astrocytic reactivity. Those findings were also described in the team's article, and they furthermore earned Julien Valette a new ERC grant to determine if diffusion-weighted NMR spectroscopy is able to measure cellular lactate compartmentalization (including in humans, using the 11.7-tesla MRI at NeuroSpin).

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