A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation
In: PLoS ONE PLoS ONE, 2017, 12 (4), pp.e0174990. ⟨10.1371/journal.pone.0174990⟩ PLoS ONE, Public Library of Science, Jg. 12 (2017-04-07), Heft 4, p e0174990
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Zugriff:
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.
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A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation
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Autor/in / Beteiligte Person: | Mazuel, Leslie ; Blanc, Jordy ; Repond, Cendrine ; Bouchaud, Véronique ; Raffard, Gérard ; Déglon, Nicole ; Bonvento, Gilles ; Pellerin, Luc ; Bouzier-Sore, Anne-Karine ; Imagerie Moléculaire et Stratégies Théranostiques (IMoST) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]) ; Centre de résonance magnétique des systèmes biologiques (CRMSB) ; Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) ; Department of Physiology ; Université de Lausanne = University of Lausanne (UNIL) ; Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN) ; Service MIRCEN (MIRCEN) ; Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB) ; Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS) ; Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB) ; Université de Lausanne (UNIL) ; Institut de Biologie François JACOB (JACOB) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS) ; Université Paris-Saclay-Institut de Biologie François JACOB (JACOB) |
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Zeitschrift: | PLoS ONE PLoS ONE, 2017, 12 (4), pp.e0174990. ⟨10.1371/journal.pone.0174990⟩ PLoS ONE, Public Library of Science, Jg. 12 (2017-04-07), Heft 4, p e0174990 |
Veröffentlichung: | HAL CCSD, 2017 |
Medientyp: | unknown |
ISSN: | 1932-6203 (print) |
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