Author
Listed:
- Daniel Jimenez-Blasco
(University of Salamanca, CSIC
Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
University Hospital of Salamanca, University of Salamanca, CSIC)
- Arnau Busquets-Garcia
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux
Integrative Pharmacology and Systems Neuroscience, IMIM Hospital del Mar Medical Research Institute)
- Etienne Hebert-Chatelain
(Université de Moncton
Université de Moncton)
- Roman Serrat
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Carlos Vicente-Gutierrez
(University of Salamanca, CSIC
Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
University Hospital of Salamanca, University of Salamanca, CSIC)
- Christina Ioannidou
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Paula Gómez-Sotres
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Irene Lopez-Fabuel
(University of Salamanca, CSIC
Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
University Hospital of Salamanca, University of Salamanca, CSIC)
- Monica Resch-Beusher
(University of Salamanca, CSIC
Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
University Hospital of Salamanca, University of Salamanca, CSIC)
- Eva Resel
(Complutense University
Instituto de Salud Carlos III)
- Dorian Arnouil
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Dave Saraswat
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Marjorie Varilh
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Astrid Cannich
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Francisca Julio-Kalajzic
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Itziar Bonilla-Del Río
(University of the Basque Country (UPV/EHU)
Science Park of the UPV/EHU)
- Angeles Almeida
(University of Salamanca, CSIC
University Hospital of Salamanca, University of Salamanca, CSIC)
- Nagore Puente
(University of the Basque Country (UPV/EHU)
Science Park of the UPV/EHU)
- Svein Achicallende
(University of the Basque Country (UPV/EHU)
Science Park of the UPV/EHU)
- Maria-Luz Lopez-Rodriguez
(Complutense University)
- Charlotte Jollé
(University of Lausanne)
- Nicole Déglon
(University of Lausanne)
- Luc Pellerin
(University of Lausanne
CNRS-University of Bordeaux
University of Poitiers)
- Charlène Josephine
(Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives)
- Gilles Bonvento
(Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives)
- Aude Panatier
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Beat Lutz
(University Medical Center
Leibniz Institute for Resilience Research (LIR))
- Pier-Vincenzo Piazza
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux
Aelis Farma)
- Manuel Guzmán
(Complutense University
Instituto de Salud Carlos III)
- Luigi Bellocchio
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
- Anne-Karine Bouzier-Sore
(CNRS-University of Bordeaux)
- Pedro Grandes
(University of the Basque Country (UPV/EHU)
Science Park of the UPV/EHU
University of Victoria)
- Juan P. Bolaños
(University of Salamanca, CSIC
Centro de Investigación Biomédica en Red sobre Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III
University Hospital of Salamanca, University of Salamanca, CSIC)
- Giovanni Marsicano
(INSERM, U1215 NeuroCentre Magendie
University of Bordeaux)
Abstract
Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses1–5. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors5–7. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB1) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB1 receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB1 receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice.
Suggested Citation
Daniel Jimenez-Blasco & Arnau Busquets-Garcia & Etienne Hebert-Chatelain & Roman Serrat & Carlos Vicente-Gutierrez & Christina Ioannidou & Paula Gómez-Sotres & Irene Lopez-Fabuel & Monica Resch-Beushe, 2020.
"Glucose metabolism links astroglial mitochondria to cannabinoid effects,"
Nature, Nature, vol. 583(7817), pages 603-608, July.
Handle:
RePEc:nat:nature:v:583:y:2020:i:7817:d:10.1038_s41586-020-2470-y
DOI: 10.1038/s41586-020-2470-y
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Cited by:
- Yuto Hasegawa & Juhyun Kim & Gianluca Ursini & Yan Jouroukhin & Xiaolei Zhu & Yu Miyahara & Feiyi Xiong & Samskruthi Madireddy & Mizuho Obayashi & Beat Lutz & Akira Sawa & Solange P. Brown & Mikhail V, 2023.
"Microglial cannabinoid receptor type 1 mediates social memory deficits in mice produced by adolescent THC exposure and 16p11.2 duplication,"
Nature Communications, Nature, vol. 14(1), pages 1-19, December.
- Weihua Ding & Liuyue Yang & Eleanor Shi & Bowon Kim & Sarah Low & Kun Hu & Lei Gao & Ping Chen & Wei Ding & David Borsook & Andrew Luo & Jee Hyun Choi & Changning Wang & Oluwaseun Akeju & Jun Yang & C, 2023.
"The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption,"
Nature Communications, Nature, vol. 14(1), pages 1-13, December.
- Nathan Fearby & Samantha Penman & Panayotis Thanos, 2022.
"Effects of Δ9-Tetrahydrocannibinol (THC) on Obesity at Different Stages of Life: A Literature Review,"
IJERPH, MDPI, vol. 19(6), pages 1-28, March.
- Albert Stuart Reece & Gary Kenneth Hulse, 2022.
"Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis,"
IJERPH, MDPI, vol. 19(24), pages 1-57, December.
- Paula Gómez-Sotres & Urszula Skupio & Tommaso Dalla Tor & Francisca Julio-Kalajzic & Astrid Cannich & Doriane Gisquet & Itziar Bonilla-Del Rio & Filippo Drago & Nagore Puente & Pedro Grandes & Luigi B, 2024.
"Olfactory bulb astrocytes link social transmission of stress to cognitive adaptation in male mice,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
- Ignacio Fernández-Moncada & Gianluca Lavanco & Unai B. Fundazuri & Nasrin Bollmohr & Sarah Mountadem & Tommaso Dalla Tor & Pauline Hachaguer & Francisca Julio-Kalajzic & Doriane Gisquet & Roman Serrat, 2024.
"A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice,"
Nature Communications, Nature, vol. 15(1), pages 1-17, December.
- Kirsten Bohmbach & Nicola Masala & Eva M. Schönhense & Katharina Hill & André N. Haubrich & Andreas Zimmer & Thoralf Opitz & Heinz Beck & Christian Henneberger, 2022.
"An astrocytic signaling loop for frequency-dependent control of dendritic integration and spatial learning,"
Nature Communications, Nature, vol. 13(1), pages 1-17, December.
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