A neuronal MCT2 knockdown in the rat somatosensory cortex reduces both the NMR lactate signal and the BOLD response during whisker stimulation
Year: 2017
Type: article
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.
Source: PLoS ONE
Institutions: Centre National de la Recherche Scientifique, Université de Bordeaux, Centre de Résonance Magnétique des Systèmes Biologiques, Centre Hospitalier Universitaire Vaudois, Université Paris-Sud, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Université Paris-Saclay, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,524
Awards: G2018443316, G471331628, G5153591501, G7240651115, G7376787254, An in vivo exploration of the metabolic coupling between glial cells and neurons upon cerebral activation and its importance for synaptic plasticity using cutting edge NMR spectroscopy approaches, G8068435768, Translational Research and Advanced Imaging Laboratory, An in vivo exploration of the metabolic coupling between glial cells and neurons upon cerebral activation and its importance for synaptic plasticity using cutting edge NMR spectroscopy approaches
OpenAlex ID: W2605202107