Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke
Abstract Brain activity relies on a steady supply of blood glucose. Astrocytes express glucose transporter 1 (GLUT1), considered their primary route for glucose uptake to sustain metabolic and antioxidant support for neurons. While GLUT1 deficiency causes severe developmental impairments, its role i...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59400-2 |
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| author | Laetitia Thieren Henri S. Zanker Jeanne Droux Urvashi Dalvi Matthias T. Wyss Rebecca Waag Pierre-Luc Germain Lukas M. von Ziegler Zoe J. Looser Ladina Hösli Luca Ravotto E. Dale Abel Johannes Bohacek Susanne Wegener L. Felipe Barros Mohamad El Amki Bruno Weber Aiman S. Saab |
| author_facet | Laetitia Thieren Henri S. Zanker Jeanne Droux Urvashi Dalvi Matthias T. Wyss Rebecca Waag Pierre-Luc Germain Lukas M. von Ziegler Zoe J. Looser Ladina Hösli Luca Ravotto E. Dale Abel Johannes Bohacek Susanne Wegener L. Felipe Barros Mohamad El Amki Bruno Weber Aiman S. Saab |
| author_sort | Laetitia Thieren |
| collection | DOAJ |
| description | Abstract Brain activity relies on a steady supply of blood glucose. Astrocytes express glucose transporter 1 (GLUT1), considered their primary route for glucose uptake to sustain metabolic and antioxidant support for neurons. While GLUT1 deficiency causes severe developmental impairments, its role in adult astrocytes remains unclear. Here, we show that astrocytes and neurons tolerate the inducible, astrocyte-specific deletion of GLUT1 in adulthood. Sensorimotor and memory functions remain intact in male GLUT1 cKO mice, indicating that GLUT1 loss does not impair behavior. Despite GLUT1 loss, two-photon glucose sensor imaging reveals that astrocytes maintain normal resting glucose levels but exhibit a more than two-fold increase in glucose consumption, indicating enhanced metabolic activity. Notably, male GLUT1 cKO mice display reduced infarct volumes following stroke, suggesting a neuroprotective effect of increased astrocytic glucose metabolism. Our findings reveal metabolic adaptability in astrocytes, ensuring glucose uptake and neuronal support despite the absence of their primary transporter. |
| format | Article |
| id | doaj-art-4adcde6adaa24da0a71035d4cf3075c2 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-4adcde6adaa24da0a71035d4cf3075c22025-08-20T01:49:48ZengNature PortfolioNature Communications2041-17232025-05-0116111510.1038/s41467-025-59400-2Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to strokeLaetitia Thieren0Henri S. Zanker1Jeanne Droux2Urvashi Dalvi3Matthias T. Wyss4Rebecca Waag5Pierre-Luc Germain6Lukas M. von Ziegler7Zoe J. Looser8Ladina Hösli9Luca Ravotto10E. Dale Abel11Johannes Bohacek12Susanne Wegener13L. Felipe Barros14Mohamad El Amki15Bruno Weber16Aiman S. Saab17University of Zurich, Institute of Pharmacology and ToxicologyUniversity of Zurich, Institute of Pharmacology and ToxicologyNeuroscience Center Zurich, University and ETH ZurichUniversity of Zurich, Institute of Pharmacology and ToxicologyUniversity of Zurich, Institute of Pharmacology and ToxicologyNeuroscience Center Zurich, University and ETH ZurichNeuroscience Center Zurich, University and ETH ZurichNeuroscience Center Zurich, University and ETH ZurichUniversity of Zurich, Institute of Pharmacology and ToxicologyUniversity of Zurich, Institute of Pharmacology and ToxicologyUniversity of Zurich, Institute of Pharmacology and ToxicologyDepartment of Medicine, David Geffen School of Medicine at UCLANeuroscience Center Zurich, University and ETH ZurichNeuroscience Center Zurich, University and ETH ZurichCentro de Estudios Científicos (CECs)Neuroscience Center Zurich, University and ETH ZurichUniversity of Zurich, Institute of Pharmacology and ToxicologyUniversity of Zurich, Institute of Pharmacology and ToxicologyAbstract Brain activity relies on a steady supply of blood glucose. Astrocytes express glucose transporter 1 (GLUT1), considered their primary route for glucose uptake to sustain metabolic and antioxidant support for neurons. While GLUT1 deficiency causes severe developmental impairments, its role in adult astrocytes remains unclear. Here, we show that astrocytes and neurons tolerate the inducible, astrocyte-specific deletion of GLUT1 in adulthood. Sensorimotor and memory functions remain intact in male GLUT1 cKO mice, indicating that GLUT1 loss does not impair behavior. Despite GLUT1 loss, two-photon glucose sensor imaging reveals that astrocytes maintain normal resting glucose levels but exhibit a more than two-fold increase in glucose consumption, indicating enhanced metabolic activity. Notably, male GLUT1 cKO mice display reduced infarct volumes following stroke, suggesting a neuroprotective effect of increased astrocytic glucose metabolism. Our findings reveal metabolic adaptability in astrocytes, ensuring glucose uptake and neuronal support despite the absence of their primary transporter.https://doi.org/10.1038/s41467-025-59400-2 |
| spellingShingle | Laetitia Thieren Henri S. Zanker Jeanne Droux Urvashi Dalvi Matthias T. Wyss Rebecca Waag Pierre-Luc Germain Lukas M. von Ziegler Zoe J. Looser Ladina Hösli Luca Ravotto E. Dale Abel Johannes Bohacek Susanne Wegener L. Felipe Barros Mohamad El Amki Bruno Weber Aiman S. Saab Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke Nature Communications |
| title | Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| title_full | Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| title_fullStr | Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| title_full_unstemmed | Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| title_short | Astrocytic GLUT1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| title_sort | astrocytic glut1 deletion in adult mice enhances glucose metabolism and resilience to stroke |
| url | https://doi.org/10.1038/s41467-025-59400-2 |
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