Morphological and functional alterations of astrocytes following experimental induced epilepsy

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Vargas, Jay R.
Title Morphological and functional alterations of astrocytes following experimental induced epilepsy
Date 2011-12
Description The mammalian central nervous system is comprised of a collection of cell types that include a variety of neuronal, glial, and blood vessel epithelial cells. The coordinated function of these cell types sustains neurotransmission and normal brain function. During the pathology of epilepsy, normal brain function is perturbed, resulting in spontaneous seizure activity. Historically, epilepsy research has focused mainly on the dysfunction of neuronal cell types. More recently, non-neuronal cell types have become implicated in the disease progression of epilepsy as well as other neurological disorders. The glial cells, and especially astrocytes, have gained the greatest attention. Once thought of merely as passive support cells, astrocytes are now known to be active participants of neurotransmission in the brain, thus making their study during epileptogenesis vital to better understanding the concerted series of events that leads to seizure activity in the epileptic brain. Using a chemoconvulsive status epilepticus (SE) model of temporal lobe epilepsy (TLE) we show multiple morphological and functional alterations of reactive astrocytes. One week following SE we observed pronounced astrogliosis accompanied by the increased expression of glial fibrillary acid protein, increased gap junction coupling accompanied by the dramatic increase of Cx43 expression, and the intact buffering ability of important extracellular constituents like potassium and glutamate. Furthermore, reactive hippocampal astrocytes begin to express specific kainate receptor (KAR) subunits following SE, as measured by immunohistochemistry and colocalization analysis. In the CA1 region of the hippocampus, GluK1, GluK2/3, GluK4 and GluK5 subunit expression was observed in GFAP positive astrocytes during the latent period 1 week following SE. At 8 weeks following SE, a time point when spontaneous behavioral iv seizures occur, the GluK1 and GluK5 subunits retained elevated expression at significant levels. KAR subunit expression in astrocytes appears to be restricted to the hippocampus and surrounding cortex. The immunohistochemistry results were corroborated using Western blotting on enriched astroglial fractions isolated from hippocampus. GluK4 receptor subunit expression was shown to be significantly increased in animals that experienced SE compared to age matched control animals. While some of the alterations observed in astrocytes during the latent period might serve as a compensatory mechanism to reduce hyperexcitability, the potential expression of functioning KARs, in conjunction with astrogliosis, may contribute substantially to hyperexcitability, synchronization, and seizure generation in TLE.
Type Text
Publisher University of Utah
Subject MESH Synaptic Transmission; Epilepsy; Astrocytes; Status Epilepticus; Epilepsy, Temporal Lobe; Models, Animal; Neurogenesis; Receptors, Kainic Acid; Hippocampus; Excitatory Amino Acid Transporter 2; Neuronal Plasticity
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of Morphological and Functional Alterations of Astrocytes Following Experimental Induced Epilepsy. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Jay R. Vargas 2011
Format Medium application/pdf
Format Extent 5,632,632 bytes
Source Original in Marriott Library Special Collections,
ARK ark:/87278/s61z7cn6
Setname ir_etd
ID 196514
Reference URL https://collections.lib.utah.edu/ark:/87278/s61z7cn6
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