Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling.
Microglia cells are the resident macrophages of the CNS, and their activation plays a critical role in inflammatory reactions associated with many brain disorders, including ischemia, Alzheimer's and Parkinson's diseases, and epilepsy. However, the changes of microglia functional properties in epilepsy have rarely been studied. Here, we used a model of status epilepticus (SE) induced by intraperitoneal kainate injections to characterize the properties of microglial cells in hippocampal slices from CX3CR1(eGFP/+) mice. SE induced within 3 h an increased expression of inflammatory mediators in the hippocampus, followed by a modification of microglia morphology, a microglia proliferation, and a significant neurodegeneration in CA1. Changes in electrophysiological intrinsic membrane properties of hippocampal microglia were detected at 24-48 h after SE with, in particular, the appearance of new voltage-activated potassium currents. Consistent with the observation of an upregulation of purinergic receptor mRNAs in the hippocampus, we also provide pharmacological evidence that microglia membrane currents mediated by the activation of P2 receptors, including P2X(7), P2Y(6), and P2Y(12), were increased 48 h after SE. As a functional consequence of this modification of purinergic signaling, motility of microglia processes toward a source of P2Y(12) receptor agonist was twice as fast in the epileptic hippocampus. This study is the first functional description of microglia activation in an in vivo model of inflammation and provides evidence for the existence of a particular microglial activation state after a status epilepticus.
Avignone
Elena
E
Inserm U603, Université Paris Descartes, Unité Mixte de Recherche-S603, Centre National de la Recherche Scientifique UMR 8154, 75006 Paris, France.
Ulmann
Lauriane
L
Levavasseur
Françoise
F
Rassendren
François
F
Audinat
Etienne
E
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D005452:Fluoresceins; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D066298:In Vitro Techniques; D007608:Kainic Acid; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000502:physiology*; D009930:Organic Chemicals; D018408:Patch-Clamp Techniques; D011687:Purines / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000235:genetics; D011983:Receptors, Purinergic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D005452:Fluoresceins; D009930:Organic Chemicals; D011687:Purines; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D011983:Receptors, Purinergic; D013873:Thionucleotides; C485184:enhanced green fluorescent protein; C435731:fluoro jade; D049452:Green Fluorescent Proteins; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D007608:Kainic Acid; C030985:purine
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