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9 results on '"Benjamin Le Gac"'

1. Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis

Author

Cuong Pham, Yuji Komaki, Anna Deàs-Just, Benjamin Le Gac, Christine Mouffle, Clara Franco, Agnès Chaperon, Vincent Vialou, Tomokazu Tsurugizawa, Bruno Cauli, and Dongdong Li

Subjects
AQP4, swelling, diffusion, Medicine, Science, Biology (General), QH301-705.5
Abstract

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood. We report that astrocyte aquaporin 4 (AQP4) mediates a tonic water efflux in basal conditions. Acute inhibition of astrocyte AQP4 leads to intracellular water accumulation as optically resolved by fluorescence-translated imaging in acute brain slices, and in vivo by fiber photometry in mobile mice. We then show that aquaporin-mediated constant water efflux maintains astrocyte volume and osmotic equilibrium, astrocyte and neuron Ca2+ signaling, and extracellular space remodeling during optogenetically induced cortical spreading depression. Using diffusion-weighted magnetic resonance imaging (DW-MRI), we observed that in vivo inhibition of AQP4 water efflux heterogeneously disturbs brain water homeostasis in a region-dependent manner. Our data suggest that astrocyte aquaporin, though bidirectional in nature, mediates a tonic water outflow to sustain cellular and environmental equilibrium in brain parenchyma.

Published
2024
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2. Centrally expressed Cav3.2 T-type calcium channel is critical for the initiation and maintenance of neuropathic pain

Author

Sophie L Fayad, Guillaume Ourties, Benjamin Le Gac, Baptiste Jouffre, Sylvain Lamoine, Antoine Fruquière, Sophie Laffray, Laila Gasmi, Bruno Cauli, Christophe Mallet, Emmanuel Bourinet, Thomas Bessaih, Régis C Lambert, and Nathalie Leresche

Subjects
anterior pretectum, GABAergic neurons, voltage-dependent calcium channels, spared nerve injury model, parvalbumin, burst, Medicine, Science, Biology (General), QH301-705.5
Abstract

Cav3.2 T-type calcium channel is a major molecular actor of neuropathic pain in peripheral sensory neurons, but its involvement at the supraspinal level is almost unknown. In the anterior pretectum (APT), a hub of connectivity of the somatosensory system involved in pain perception, we show that Cav3.2 channels are expressed in a subpopulation of GABAergic neurons coexpressing parvalbumin (PV). In these PV-expressing neurons, Cav3.2 channels contribute to a high-frequency-bursting activity, which is increased in the spared nerve injury model of neuropathy. Specific deletion of Cav3.2 channels in APT neurons reduced both the initiation and maintenance of mechanical and cold allodynia. These data are a direct demonstration that centrally expressed Cav3.2 channels also play a fundamental role in pain pathophysiology.

Published
2022
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3. Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

Author

Anastassios Karagiannis, Thierry Gallopin, Alexandre Lacroix, Fabrice Plaisier, Juliette Piquet, Hélène Geoffroy, Régine Hepp, Jérémie Naudé, Benjamin Le Gac, Richard Egger, Bertrand Lambolez, Dongdong Li, Jean Rossier, Jochen F Staiger, Hiromi Imamura, Susumu Seino, Jochen Roeper, and Bruno Cauli

Subjects
brain metabolism, katp channel, neocortex, pyramidal cell, interneuron, Medicine, Science, Biology (General), QH301-705.5
Abstract

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.

Published
2021
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5. Induction of oxidative stress and alteration of synaptic gene expression in newborn hippocampal granule cells after developmental exposure to Aroclor 1254

Author

Anneline Pinson, Elena Sevrin, Christina Chatzi, Benjamin Le Gac, Marc Thiry, Gary L. Westbrook, and Anne-Simone Parent

Subjects
Cellular and Molecular Neuroscience, Endocrinology, Endocrine and Autonomic Systems, Endocrinology, Diabetes and Metabolism
Abstract

Introduction: Hippocampal newborn neurons integrate into functional circuits where they play an important role in learning and memory. We previously showed that perinatal exposure to Aroclor 1254, a commercial mixture of polychlorinated biphenyls (PCBs) associated with alterations of cognitive function in children, disrupted the normal maturation of excitatory synapses in the dentate gyrus. We hypothesized that hippocampal immature neurons underlie some of the cognitive effects of PCBs. Methods: We used newly-generated neurons to examine the effects of PCBs in mice following maternal exposure. Newborn dentate granule cells were tagged with enhanced green fluorescent protein (EGFP) using a transgenic mouse line. The transcriptome of the newly generated granule cells was assessed using RNA sequencing. Results: Gestational and lactational exposure to 6 mg/kg/day of Aroclor 1254 disrupted the mRNA expression of 1308 genes in newborn granule cells. Genes involved in mitochondrial functions were highly enriched with 154 genes significantly increased in exposed compared to control mice. The upregulation of genes involved in oxidative phosphorylation was accompanied by signs of endoplasmic reticulum stress and an increase in lipid peroxidation, a marker of oxidative stress, in the subgranular zone of the dentate gyrus but not in mature granule cells in the granular zone. Aroclor 1254 exposure also disrupted the expression of synaptic genes. Using laser-captured subgranular and granular zones, this effect was restricted to the subgranular zone, where newborn neurons are located. Conclusion: Our data suggest that gene expression in newborn granule cells is disrupted by Aroclor 1254 and provide clues to the effects of endocrine disrupting chemicals on the brain.

Published
2022
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6. Lactate is an energy substrate for rodent cortical neurons and enhances their firing activity

Author

Jérémie Naudé, Juliette Piquet, Bertrand Lambolez, Alexandre Lacroix, Jean Rossier, Bruno Cauli, Anastassios Karagiannis, Dongdong Li, Benjamin Le Gac, Régine Hepp, Thierry Gallopin, Hiromi Imamura, Richard Egger, Hélène Geoffroy, Fabrice Plaisier, Susumu Seino, Jochen F. Staiger, Jochen Roeper, Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Goethe-University Frankfurt am Main, Georg-August-University = Georg-August-Universität Göttingen, Kyoto University [Kyoto], Kobe University, Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Göttingen - Georg-August-Universität Göttingen, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Kyoto University, and HAL-SU, Gestionnaire

Subjects
Male, Mouse, Rodent, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Oxidative Phosphorylation, Adenosine Triphosphate, 0302 clinical medicine, KATP Channels, neocortex, Premovement neuronal activity, Glycolysis, Biology (General), Cerebral Cortex, Neurons, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Neocortex, biology, Chemistry, General Neuroscience, General Medicine, Cell biology, Crosstalk (biology), medicine.anatomical_structure, Cerebral cortex, Medicine, Research Article, QH301-705.5, Science, Oxidative phosphorylation, interneuron, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, biology.animal, medicine, Animals, Lactic Acid, Rats, Wistar, katp channel, 030304 developmental biology, pyramidal cell, General Immunology and Microbiology, Substrate (chemistry), Mice, Inbred C57BL, Glucose, nervous system, brain metabolism, Rat, Energy Metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Neuroscience
Abstract

Glucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with KCNJ11 and ABCC8 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.

Published
2021
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7. Lactate is a major energy substrate for cortical neurons and enhances their firing activity

Author

Dongdong Li, Anastassios Karagiannis, Benjamin Le Gac, Jean Rossier, Bruno Cauli, Richard Egger, Alexandre Lacroix, Susumu Seino, Jochen F. Staiger, Juliette Piquet, Hélène Geoffroy, Jochen Roeper, Hiromi Imamura, Jérémie Naudé, Fabrice Plaisier, Régine Hepp, Thierry Gallopin, Bertrand Lambolez, Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Plasticité du Cerveau Brain Plasticity (UMR 8249) (PdC), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Goethe-University Frankfurt am Main, University Medical Center Göttingen (UMG), Kyoto University [Kyoto], Kobe University, Cauli, Bruno, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Kyoto University

Subjects
0303 health sciences, endocrine system, Neocortex, Chemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Substrate (chemistry), Oxidative phosphorylation, Cortical neurons, Cell biology, 03 medical and health sciences, Crosstalk (biology), 0302 clinical medicine, medicine.anatomical_structure, nervous system, Cerebral cortex, medicine, Premovement neuronal activity, Glycolysis, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

SummaryGlucose is the mandatory fuel for the brain, yet the relative contribution of glucose and lactate for neuronal energy metabolism is unclear. We found that increased lactate, but not glucose concentration, enhances the spiking activity of neurons of the cerebral cortex. Enhanced spiking was dependent on ATP-sensitive potassium (KATP) channels formed with Kir6.2 and SUR1 subunits, which we show are functionally expressed in most neocortical neuronal types. We also demonstrate the ability of cortical neurons to take-up and metabolize lactate. We further reveal that ATP is produced by cortical neurons largely via oxidative phosphorylation and only modestly by glycolysis. Our data demonstrate that in active neurons, lactate is preferred to glucose as an energy substrate, and that lactate metabolism shapes neuronal activity in the neocortex through KATP channels. Our results highlight the importance of metabolic crosstalk between neurons and astrocytes for brain function.HighlightsMost cortical neurons subtypes express pancreatic beta-cell like KATP channels.Lactate enhances spiking activity via its uptake and closure of KATP channels.Cortical neurons take up and oxidize lactate.Cortical neurons produce ATP mainly by oxidative phosphorylation.

Published
2021

9. Single Cell Multiplex Reverse Transcription Polymerase Chain Reaction After Patch-clamp

Author

Gabrielle Devienne, Juliette Piquet, Benjamin Le Gac, Bruno Cauli, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Cell type, Patch-Clamp Techniques, General Chemical Engineering, Cell, neurons, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Multiplex polymerase chain reaction, medicine, Multiplex, Gene, General Immunology and Microbiology, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, astrocytes, Reverse Transcription, Gene expression profile, brain slices, Reverse transcription polymerase chain reaction, 030104 developmental biology, medicine.anatomical_structure, Cytoplasm, Transcriptome, Multiplex Polymerase Chain Reaction, whole-cell configuration, 030217 neurology & neurosurgery, Intracellular, Neuroscience, nested polymerase chain reaction (PCR)
Abstract

International audience; The cerebral cortex is composed of numerous cell types exhibiting various morphological, physiological, and molecular features. This diversity hampers easy identification and characterization of these cell types, prerequisites to study their specific functions. This article describes the multiplex single cell reverse transcription polymerase chain reaction (RT-PCR) protocol, which allows, after patch-clamp recording in slices, to detect simultaneously the expression of tens of genes in a single cell. This simple method can be implemented with morphological characterization and is widely applicable to determine the phenotypic traits of various cell types and their particular cellular environment, such as in the vicinity of blood vessels. The principle of this protocol is to record a cell with the patch-clamp technique, to harvest and reverse transcribe its cytoplasmic content, and to detect qualitatively the expression of a predefined set of genes by multiplex PCR. It requires a careful design of PCR primers and intracellular patch-clamp solution compatible with RT-PCR. To ensure a selective and reliable transcript detection, this technique also requires appropriate controls from cytoplasm harvesting to amplification steps. Although precautions discussed here must be strictly followed, virtually any electrophysiological laboratory can use the multiplex single cell RT-PCR technique.

Published
2018
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