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Cover for Acute Microglial Responses to Single Non-Epileptogenic vs. Epileptogenic Seizures in Mouse Hippocampus
dc.contributor.advisorVicini, Stefano
dc.creator
dc.date.accessioned2019-09-16T17:54:08Z
dc.date.available2019-09-16T17:54:08Z
dc.date.created2019
dc.date.issued
dc.date.submitted01/01/2019
dc.identifier.uri
dc.descriptionPh.D.
dc.description.abstractAs the resident macrophage of the central nervous system, microglia are in a uniquely privileged position to both affect and be affected by neuroinflammation, neuronal activity and injury, which are all hallmarks of seizures and the epilepsies. In one of the prototypical rodent models of seizure-induced epilepsy, hippocampal microglia become activated after prolonged, damaging seizures known as Status Epilepticus (SE). However, since SE comprises both neuronal hyperactivity and injury, the specific mechanisms triggering this microglial activation remain unclear, as does its relevance to the ensuing epileptogenic processes.
dc.description.abstractThe present studies employed another well-established seizure model, electroconvulsive shock (ECS), to study the effect of paroxysmal/ictal neuronal hyperactivity on mouse hippocampal microglia, in the absence ofconcomitant neuronal degeneration. Unlike SE, ECS did not cause neuronal injury and did not alter hippocampal CA1 microglial and astrocytic density, morphology nor baseline process 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 CCL2. As opposed to the general pro-inflammatory environment produced after SE (where induction of CCL2,TNF, IL-1and IL-6 signaling among others have been reported), the acute microglial response to ECS was more selective: I found upregulated expression of Ccl2 message but unchanged transcript levels of the pro-inflammatory cytokine Tnf. 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.
dc.description.abstractThis differs from previously described alterations in intrinsic characteristics and purinoreceptor upregulation which coincided with enhanced purinergic currents following SE. These ECS-induced effects point to a common “seizure signature” in hippocampal microglia, characterized by functional alterations to purinergic signaling. The data herein demonstrate that ictal activity per secan drive changes in microglial physiology. These described physiological changes (which up until now have been exclusively associated with prolonged and damaging seizures) are of added interest as they may be relevant to electroconvulsive therapy which remains a gold-standard treatment for depression.
dc.formatPDF
dc.format.extent206 leaves
dc.languageen
dc.publisherGeorgetown University
dc.sourceGeorgetown University-Graduate School of Arts & Sciences
dc.sourceNeuroscience
dc.subjectATP
dc.subjectbrain
dc.subjectCX3CR1
dc.subjectepilepsy
dc.subjectGFP
dc.subjectpurinergic
dc.subject.lcshNeurosciences
dc.subject.otherNeurosciences
dc.titleAcute Microglial Responses to Single Non-Epileptogenic vs. Epileptogenic Seizures in Mouse Hippocampus
dc.typethesis
dc.identifier.orcid/0000-0002-6479-8635


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