1. Ketamine/xylazine and barbiturates modulate microglial morphology and motility differently in a mouse model
- Author
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Ines Hristovska, Fabrice Chrétien, Franck Verdonk, Eileen S. Tsai, Jean-Christophe Comte, Jérôme Honnorat, Virginie Desestret, Olivier Pascual, Bodescot, Myriam, Régulation de la plasticité synaptique par les microglies : un travail de nuit ? - - Micromem2017 - ANR-17-CE16-0008 - AAPG2017 - VALID, Synaptopathies et Autoanticorps [Lyon] (SynatAc), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Forgetting Processes and Cortical Dynamics (FORGETTING), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence Maladie Rare 'Syndromes neurologiques Paranéoplasiques', Hospices Civils de Lyon (HCL)-Hopital Neurologique, Université Sorbonne Paris Cité (USPC), Laboratoire Hospitalo-Universitaire de Neuropathologie [Paris], Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IH was funded by the French ministry for research. This work was also supported by the Foundation des Gueules Cassées and the SFAR (Société Française d’Anesthésie-Réanimation), ANR MICROMEM # R17136CC and INSERM., ANR-17-CE16-0008,Micromem,Régulation de la plasticité synaptique par les microglies : un travail de nuit ?(2017), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Université de Paris (UP), Processus d'oubli et Dynamique Corticale [Lyon], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,Xylazine ,0301 basic medicine ,Cytoplasm ,Physiology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Hippocampus ,Mice ,0302 clinical medicine ,Animal Cells ,Anesthesiology ,Cell Movement ,Medicine and Health Sciences ,Premovement neuronal activity ,Anesthesia ,Pentobarbital ,Clinical Neurophysiology ,Brain Mapping ,Multidisciplinary ,Microglia ,Pharmaceutics ,Chemistry ,Drugs ,Brain ,Electroencephalography ,Electrophysiology ,Cell Motility ,Bioassays and Physiological Analysis ,medicine.anatomical_structure ,Brain Electrophysiology ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Medicine ,Ketamine ,Cellular Types ,Anatomy ,Cellular Structures and Organelles ,Research Article ,medicine.drug ,Imaging Techniques ,Science ,Neurophysiology ,Motility ,Glial Cells ,Neuroimaging ,Mice, Transgenic ,Research and Analysis Methods ,Receptors, N-Methyl-D-Aspartate ,03 medical and health sciences ,Drug Therapy ,In vivo ,medicine ,Pain Management ,Animals ,Thiopental ,GABA Modulators ,Microglial Cells ,Anesthetics ,Pharmacology ,Electrophysiological Techniques ,Neurotoxicity ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Biology and Life Sciences ,Cell Biology ,medicine.disease ,030104 developmental biology ,Anesthetic ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Clinical Medicine ,Neuroscience ,030217 neurology & neurosurgery ,Ex vivo - Abstract
International audience; Microglia, the resident immune cells of the brain, are highly ramified and motile and their morphology is strongly linked to their function. Microglia constantly monitor the brain parenchyma and are crucial for maintaining brain homeostasis and fine-tuning neuronal networks. Besides affecting neurons, anesthetics may have wide-ranging effects mediated by non-neuronal cells and in particular microglia. We thus examined the effect of two commonly used anesthetic agents, ketamine/xylazine and barbiturates, on microglial motility and morphology. A combination of two-photon in vivo imaging and electroencephalography (EEG) recordings in unanesthetized and anesthetized mice as well as automated analysis of ex vivo sections were used to assess morphology and dynamics of microglia. We found that administration of ketamine/xylazine and pentobarbital anesthesia resulted in quite distinct EEG profiles. Both anesthetics reduced microglial motility, but only ketamine/xylazine administration led to reduction of microglial complexity in vivo. The change of cellular dynamics in vivo was associated with a region-dependent reduction of several features of microglial cells ex vivo, such as the complexity index and the ramification length, whereas thiopental altered the size of the cytoplasm. Our results show that anesthetics have considerable effects on neuronal activity and microglial morphodynamics and that barbiturates may be a preferred anesthetic agent for the study of microglial morphology. These findings will undoubtedly raise compelling questions about the functional relevance of anesthetics on microglial cells in neuronal physiology and anesthesia-induced neurotoxicity.
- Published
- 2020
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