Please use this identifier to cite or link to this item:
Title: Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus : implications for seizure susceptibility
Authors: Balosso, Silvia
Ravizza, Teresa Giovanna
Pierucci, Massimo
Calcagno, Eleonora
Invernizzi, Roberto William
Di Giovanni, Giuseppe
Esposito, Ennio
Vezzani, Annamaria
Keywords: Astrocytes
Receptors, Kainic acid
Issue Date: 2009
Publisher: Pergamon Press
Citation: Balosso, S., Ravizza, T., Pierucci, M., Calcagno, E., Invernizzi, R., Di Giovanni, G., Esposito, E., & Vezzani, A. (2009). Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus : implications for seizure susceptibility. Neuroscience, 161(1), 293-300.
Abstract: Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subunits while GluR1, GluR2, GluR6/7 and NR2A/B were unchanged as compared to wild-type mice. In p75(-/-) mice, GluR2, GluR3, GluR6/7 and NR2A/B glutamate receptor subunits were increased in the hippocampus while GluR1 and NR1 did not change. Extracellular single-cell recordings of the electrical activity of hippocampal neurons were carried out in anesthetized mice by standard electrophysiological techniques. Microiontophoretic application of glutamate increased the basal firing rate of hippocampal neurons in p75(-/-) mice versus wild-type mice, and this effect was blocked by 2-amino-5-phosphopentanoic acid and 6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione denoting the involvement of N-methyl-D-aspartic acid and AMPA receptors. In p55(-/-) mice, hippocampal neurons responses to glutamate were similar to wild-type mice. Spontaneous glutamate release measured by in vivo hippocampal microdialysis was significantly decreased only in p55(-/-) mice. No changes were observed in KCl-induced glutamate release in both receptor knockout mice strains versus wild-type mice. These findings highlight specific molecular and functional interactions between p55 and p75 receptor-mediated signaling and the glutamate system. These interactions may be relevant for controlling neuronal excitability in physiological and pathological conditions.
Appears in Collections:Scholarly Works - FacM&SPB

Files in This Item:
File Description SizeFormat 
Balosso 2009.pdf415.88 kBAdobe PDFView/Open

Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.