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Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus

Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. Hippocampal microglia become activated after prolonged, damaging seizures known as status epilepticus (SE). However, since...

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Autores principales: Sepulveda-Rodriguez, Alberto, Li, Pinggan, Khan, Tahiyana, Ma, James D., Carlone, Colby A., Bozzelli, P. Lorenzo, Conant, Katherine E., Forcelli, Patrick A., Vicini, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498419/
https://www.ncbi.nlm.nih.gov/pubmed/31058213
http://dx.doi.org/10.1523/ENEURO.0056-19.2019
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author Sepulveda-Rodriguez, Alberto
Li, Pinggan
Khan, Tahiyana
Ma, James D.
Carlone, Colby A.
Bozzelli, P. Lorenzo
Conant, Katherine E.
Forcelli, Patrick A.
Vicini, Stefano
author_facet Sepulveda-Rodriguez, Alberto
Li, Pinggan
Khan, Tahiyana
Ma, James D.
Carlone, Colby A.
Bozzelli, P. Lorenzo
Conant, Katherine E.
Forcelli, Patrick A.
Vicini, Stefano
author_sort Sepulveda-Rodriguez, Alberto
collection PubMed
description Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. Hippocampal microglia become activated after prolonged, damaging seizures known as status epilepticus (SE). However, since SE causes both hyperactivity and injury of neurons, the mechanisms triggering this activation remain unclear, as does the relevance of the microglial activation to the ensuing epileptogenic processes. In this study, we use electroconvulsive shock (ECS) to study the effect of neuronal hyperactivity without neuronal degeneration on mouse hippocampal microglia. Unlike SE, ECS did not alter hippocampal CA1 microglial density, morphology, or baseline motility. In contrast, both ECS and SE produced a similar increase in ATP-directed microglial process motility in acute slices, and similarly upregulated expression of the chemokine C-C motif chemokine ligand 2 (CCL2). Whole-cell patch-clamp recordings of hippocampal CA1sr microglia showed that ECS enhanced purinergic currents mediated by P2X7 receptors in the absence of changes in passive properties or voltage-gated currents, or changes in receptor expression. This differs from previously described alterations in intrinsic characteristics which coincided with enhanced purinergic currents following SE. These ECS-induced effects point to a “seizure signature” in hippocampal microglia characterized by altered purinergic signaling. These data demonstrate that ictal activity per se can drive alterations in microglial physiology without neuronal injury. These physiological changes, which up until now have been associated with prolonged and damaging seizures, are of added interest as they may be relevant to electroconvulsive therapy (ECT), which remains a gold-standard treatment for depression.
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spelling pubmed-64984192019-05-03 Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus Sepulveda-Rodriguez, Alberto Li, Pinggan Khan, Tahiyana Ma, James D. Carlone, Colby A. Bozzelli, P. Lorenzo Conant, Katherine E. Forcelli, Patrick A. Vicini, Stefano eNeuro New Research Microglia are in a privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. Hippocampal microglia become activated after prolonged, damaging seizures known as status epilepticus (SE). However, since SE causes both hyperactivity and injury of neurons, the mechanisms triggering this activation remain unclear, as does the relevance of the microglial activation to the ensuing epileptogenic processes. In this study, we use electroconvulsive shock (ECS) to study the effect of neuronal hyperactivity without neuronal degeneration on mouse hippocampal microglia. Unlike SE, ECS did not alter hippocampal CA1 microglial density, morphology, or baseline motility. In contrast, both ECS and SE produced a similar increase in ATP-directed microglial process motility in acute slices, and similarly upregulated expression of the chemokine C-C motif chemokine ligand 2 (CCL2). Whole-cell patch-clamp recordings of hippocampal CA1sr microglia showed that ECS enhanced purinergic currents mediated by P2X7 receptors in the absence of changes in passive properties or voltage-gated currents, or changes in receptor expression. This differs from previously described alterations in intrinsic characteristics which coincided with enhanced purinergic currents following SE. These ECS-induced effects point to a “seizure signature” in hippocampal microglia characterized by altered purinergic signaling. These data demonstrate that ictal activity per se can drive alterations in microglial physiology without neuronal injury. These physiological changes, which up until now have been associated with prolonged and damaging seizures, are of added interest as they may be relevant to electroconvulsive therapy (ECT), which remains a gold-standard treatment for depression. Society for Neuroscience 2019-04-23 /pmc/articles/PMC6498419/ /pubmed/31058213 http://dx.doi.org/10.1523/ENEURO.0056-19.2019 Text en Copyright © 2019 Sepulveda-Rodriguez et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Sepulveda-Rodriguez, Alberto
Li, Pinggan
Khan, Tahiyana
Ma, James D.
Carlone, Colby A.
Bozzelli, P. Lorenzo
Conant, Katherine E.
Forcelli, Patrick A.
Vicini, Stefano
Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title_full Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title_fullStr Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title_full_unstemmed Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title_short Electroconvulsive Shock Enhances Responsive Motility and Purinergic Currents in Microglia in the Mouse Hippocampus
title_sort electroconvulsive shock enhances responsive motility and purinergic currents in microglia in the mouse hippocampus
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498419/
https://www.ncbi.nlm.nih.gov/pubmed/31058213
http://dx.doi.org/10.1523/ENEURO.0056-19.2019
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