title: A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation.
abstract: Although several in vitro and ex vivo evidence support the existence of lactate exchange between astrocytes and neurons, a direct demonstration in vivo is still lacking. In the present study, a lentiviral vector carrying a short hairpin RNA (shRNA) was used to downregulate the expression of the monocarboxylate transporter type 2 (MCT2) in neurons of the rat somatosensory cortex (called S1BF) by ~ 25%. After one hour of whisker stimulation, HRMAS 1H-NMR spectroscopy analysis of S1BF perchloric acid extracts showed that while an increase in lactate content is observed in both uninjected and shRNA-control injected extracts, such an effect was abrogated in shMCT2 injected rats. A 13C-incorporation analysis following [1-13C]glucose infusion during the stimulation confirmed that the elevated lactate observed during activation originates from newly synthesized [3-13C]lactate, with blood-derived [1-13C]glucose being the precursor. Moreover, the analysis of the 13C-labeling of glutamate in position C3 and C4 indicates that upon activation, there is an increase in TCA cycle velocity for control rats while a decrease is observed for MCT2 knockdown animals. Using in vivo localized 1H-NMR spectroscopy, an increase in lactate levels is observed in the S1BF area upon whisker stimulation for shRNA-control injected rats but not for MCT2 knockdown animals. Finally, while a robust BOLD fMRI response was evidenced in control rats, it was absent in MCT2 knockdown rats. These data not only demonstrate that glucose-derived lactate is locally produced following neuronal activation but also suggest that its use by neurons via MCT2 is probably essential to maintain synaptic activity within the barrel cortex.
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Mazuel
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.
authors.forename: Jordy
authors.initials: J
authors.lastname: Blanc
authors.affiliation: Département de Physiologie, 7 rue du Bugnon, CH Lausanne, Switzerland.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Repond
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Bouchaud
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Raffard
authors.affiliation: Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, Lausanne, Switzerland.|Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Déglon
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Département de la Recherche Fondamentale (DRF), Institut d'Imagerie Biomédicale (I2BM), Molecular Imaging Center (MIRCen), CNRS UMR 9199, Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.|Département de Physiologie, 7 rue du Bugnon, CH Lausanne, Switzerland.
authors.forename: Luc
authors.initials: L
authors.lastname: Pellerin
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques UMR 5536, CNRS-Université Bordeaux 146 rue Léo-Saignat, Bordeaux, France.
authors.forename: Anne-Karine
authors.initials: AK
authors.lastname: Bouzier-Sore
mesh_terms: D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D005260:Female; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors; D019344:Lactic Acid / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D008279:Magnetic Resonance Imaging; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D014738:Vibrissae
chemical_list: D027501:Monocarboxylic Acid Transporters; C091633:Slc16a7 protein, rat; D019344:Lactic Acid