Diffusion-weighted magnetic resonance spectroscopy enables cell-specific monitoring of astrocyte reactivity in vivo
Open accessPublished version of a preprint
Abstract
Reactive astrocytes exhibit hypertrophic morphology and altered metabolism. Deciphering astrocytic status would be of great importance to understand their role and dysregulation in pathologies, but most analytical methods remain highly invasive or destructive. The diffusion of brain metabolites, as non-invasively measured using diffusion-weighted magnetic resonance spectroscopy (DW-MRS) in vivo, depends on the structure of their micro-environment. Here we perform advanced DW-MRS in a mouse model of reactive astrocytes to determine how cellular compartments confining metabolite diffusion are changing. This reveals myo-inositol as a specific intra-astrocytic marker whose diffusion closely reflects astrocytic morphology, enabling non-invasive detection of astrocyte hypertrophy (subsequently confirmed by confocal microscopy ex vivo). Furthermore, we measure massive variations of lactate diffusion properties, suggesting that intracellular lactate is predominantly astrocytic under control conditions, but predominantly neuronal in case of astrocyte reactivity. This indicates massive remodeling of lactate metabolism, as lactate compartmentation is tightly linked to the astrocyte-to-neuron lactate shuttle mechanism.
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Better cellular specificity might be achieved by measuring the diffusion of cell-specific endogenous metabolites with magnetic resonance spectroscopy.
“However, better cellular specificity might be achieved by measuring the diffusion of cell-specific endogenous metabolites with magnetic resonance spectroscopy [511,512,513].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [511]
Cites
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“This would open unprecedented possibilities to study lactate metabolism and astrocyte-neuron interactions in various contexts, such as brain activity (Pellerin and Magistretti, 1994), synaptic plasticity and long-term memory (Suzuki et al.”
BackgroundResultAstrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation
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Dipy, a library for the analysis of diffusion MRI data
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Gliotransmitters Travel in Time and Space
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Neuronal Stimulation Triggers Neuronal Glycolysis and Not Lactate Uptake
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“Finally, information from the model was extracted using L-measure (Scorcioni et al., 2008).”
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Can we detect the effect of spines and leaflets on the diffusion of brain intracellular metabolites?
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Raven, E. P., Veraart, J., Kievit, R. A., Genc, S., Ward, I. L., Hall, J., Cunningham, A., Doherty, J., van den Bree, M. B. M., & Jones, D. K. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02178-w · Cited by 21 · see citing works
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Bougnères, P., & Le Stunff, C. (2025) · Genes · doi:10.3390/genes16050590 · Cited by 11 · see citing works
- Authors
- Ligneul, C., Palombo, M., Hernández-Garzón, E., Carrillo-de Sauvage, M.-A., Flament, J., Hantraye, P., Brouillet, E., Bonvento, G., Escartin, C., & Valette, J.
- Affiliations
- Université Paris-Sud (FR)
- University College London (GB)
- Inserm (FR)
- Corresponding author
- Valette, Julien
- ORCID
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 191
- Pages
- 457-469
- ISSN
- 1053-8119 (ISSN-L)
- OpenAlex
- W2949686995
- Cited by
- 77
- References
- 10
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 15 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 18 · 2019: 2
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- NeuroImage (acceptedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- European Commission (336331)
- Engineering and Physical Sciences Research Council (EP/N018702/1)
- European Research Council
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- reactive astrocytes, astrocyte hypertrophy, diffusion-weighted magnetic resonance spectroscopy, myo-inositol, lactate metabolism, astrocyte morphology, mouse model
- MeSH terms
- Animals, Astrocytes, Brain, Inositol, Male, Mice, Inbred C57BL, Magnetic Resonance Spectroscopy, Biomarkers, Lactic Acid, Diffusion Magnetic Resonance Imaging, Mice
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