Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance
| Autor: | Eduardo R. Zimmer, Imad Benkhaled, Philippe Massot, Charlotte Jollé, Hélène Roumes, Véronique Bouchaud, Nicole Déglon, Luc Pellerin, Anne-Karine Bouzier-Sore, Jordy Blanc, Marc Biran, Gérard Raffard, Carolina Piletti Chatain, Catherine Pythoud |
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| Přispěvatelé: | Centre de résonance magnétique des systèmes biologiques (CRMSB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Université de Lausanne (UNIL), Laboratoire commun Imagerie Métabolique Multi-Noyaux Multi-Organes (I3M), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Siemens Healthineers, Digital Services, Digital Technology and Innovation, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre National de la Recherche Scientifique (CNRS)-Siemens Healthineers, Digital Services, Digital Technology and Innovation, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Lausanne University Hospital, N.D. has received support from the BIOS and Panacée Foundations. I.B. is supported by the LabCom I3M, Common Laboratory CNRS-Siemens, University of Poitiers and Poitiers University Hospital and by Region Nouvelle Aquitaine. E.R.Z. is supported by Conselho Nacional de Pesquisas (CNPq) 435642/2018-9 and 312410/2018-2, Instituto Serrapilheira Serra-1912-31365, Brazilian National Institute of Science and Technology in Excitotoxicity and Neuroprotection 465671/2014-4, Fundaçao de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) / MS/CNPq/Secretaria da Saùde do Rio Grande do Sul–Programa Pesquisa para a Sus 30786.434.24734.23112017, ARD/FAPERGS 54392.632.30451.05032021, and Alzheimer’s Association AARGD-21-850670., ANR-15-CE37-0012,INNES,Exploration in vivo du couplage métabolique entre neurones et astrocytes lors de l'activation cérébrale: étude par spectroscopie de RMN(2015), ANR-10-IDEX-0003,IDEX BORDEAUX,Initiative d'excellence de l'Université de Bordeaux(2010), ANR-10-LABX-0057,TRAIL,Translational Research and Advanced Imaging Laboratory(2010), Bouzier-Sore, Anne-Karine, Exploration in vivo du couplage métabolique entre neurones et astrocytes lors de l'activation cérébrale: étude par spectroscopie de RMN - - INNES2015 - ANR-15-CE37-0012 - AAPG2015 - VALID, Initiative d'excellence de l'Université de Bordeaux - - IDEX BORDEAUX2010 - ANR-10-IDEX-0003 - IDEX - VALID, Translational Research and Advanced Imaging Laboratory - - TRAIL2010 - ANR-10-LABX-0057 - LABX - VALID |
| Rok vydání: | 2021 |
| Předmět: |
Male
Monocarboxylic Acid Transporters MRS Magnetic Resonance Spectroscopy genetic structures Hemodynamics Muscle Proteins Stimulation Brain metabolism 03 medical and health sciences 0302 clinical medicine Memory Animals Learning [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Lactic Acid Rats Wistar Multidisciplinary brain metabolism fMRI learning and memory monocarboxylate transporter 030304 developmental biology Monocarboxylate transporter Neurons 0303 health sciences Sensory stimulation therapy brain metabolis biology Chemistry Transporter Barrel cortex Biological Sciences Magnetic Resonance Imaging Peripheral Rats mmonocarboxylate transporter Oxygen Saturation Astrocytes Vibrissae biology.protein [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Energy source Neuroscience 030217 neurology & neurosurgery [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Proc Natl Acad Sci U S A Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2021, 118 (47), pp.e2112466118. ⟨10.1073/pnas.2112466118⟩ Proceedings of the National Academy of Sciences of the United States of America, 2021, 118 (47), ⟨10.1073/pnas.2112466118⟩ Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 47, pp. e2112466118 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2112466118⟩ |
| Popis: | International audience; Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation. |
| Databáze: | OpenAIRE |
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