Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo

The proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on...

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Main Authors:	Ellen D. Stück, Randolph N. Christensen, J. Russell Huie, C. Amy Tovar, Brandon A. Miller, Yvette S. Nout, Jacqueline C. Bresnahan, Michael S. Beattie, Adam R. Ferguson
Format:	Article
Language:	English
Published:	Hindawi Limited 2012-01-01
Series:	Neural Plasticity
Online Access:	http://dx.doi.org/10.1155/2012/261345

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spelling	doaj-89292cf6a78a4e80929822a2116e10ed2020-11-24T22:29:38ZengHindawi LimitedNeural Plasticity2090-59041687-54432012-01-01201210.1155/2012/261345261345Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In VivoEllen D. Stück0Randolph N. Christensen1J. Russell Huie2C. Amy Tovar3Brandon A. Miller4Yvette S. Nout5Jacqueline C. Bresnahan6Michael S. Beattie7Adam R. Ferguson8Brain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, CA 94110, USABiology Department, Coe College, Cedar Rapids, IA 52402, USABrain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, CA 94110, USADepartment of Neuroscience, The Ohio State University, Columbus, OH 43210, USADepartment of Neurological Surgery, Emory University, Atlanta, GA 30322, USAAnimal and Veterinary Sciences Department, California State Polytechnic University, Pomona, CA 91768, USABrain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, CA 94110, USABrain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, CA 94110, USABrain and Spinal Injury Center (BASIC), Department of Neurological Surgery, University of California, San Francisco, CA 94110, USAThe proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on the neuronal surface after TNFα exposure is associated with a rapid internalization of GABAA receptors (GABAARs), suggesting complex timing and dose dependency of the CNS’s response to TNFα. However, the effect of TNFα on GABAAR trafficking in vivo remains unclear. We assessed the effect of TNFα nanoinjection on rapid GABAAR changes in rats (𝑁=30) using subcellular fractionation, quantitative western blotting, and confocal microscopy. GABAAR protein levels in membrane fractions of TNFα and vehicle-treated subjects were not significantly different by Western Blot, yet high-resolution quantitative confocal imaging revealed that TNFα induces GABAAR trafficking to synapses in a dose-dependent manner by 60 min. TNFα-mediated GABAAR trafficking represents a novel target for CNS excitotoxicity.http://dx.doi.org/10.1155/2012/261345
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Ellen D. Stück Randolph N. Christensen J. Russell Huie C. Amy Tovar Brandon A. Miller Yvette S. Nout Jacqueline C. Bresnahan Michael S. Beattie Adam R. Ferguson
spellingShingle	Ellen D. Stück Randolph N. Christensen J. Russell Huie C. Amy Tovar Brandon A. Miller Yvette S. Nout Jacqueline C. Bresnahan Michael S. Beattie Adam R. Ferguson Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo Neural Plasticity
author_facet	Ellen D. Stück Randolph N. Christensen J. Russell Huie C. Amy Tovar Brandon A. Miller Yvette S. Nout Jacqueline C. Bresnahan Michael S. Beattie Adam R. Ferguson
author_sort	Ellen D. Stück
title	Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo
title_short	Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo
title_full	Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo
title_fullStr	Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo
title_full_unstemmed	Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo
title_sort	tumor necrosis factor alpha mediates gabaa receptor trafficking to the plasma membrane of spinal cord neurons in vivo
publisher	Hindawi Limited
series	Neural Plasticity
issn	2090-5904 1687-5443
publishDate	2012-01-01
description	The proinflammatory cytokine TNFα contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNFα contributes to excitotoxicity by increasing GluA2-lacking AMPA receptor (AMPAR) trafficking to the neuronal plasma membrane. In vitro, increased AMPAR on the neuronal surface after TNFα exposure is associated with a rapid internalization of GABAA receptors (GABAARs), suggesting complex timing and dose dependency of the CNS’s response to TNFα. However, the effect of TNFα on GABAAR trafficking in vivo remains unclear. We assessed the effect of TNFα nanoinjection on rapid GABAAR changes in rats (𝑁=30) using subcellular fractionation, quantitative western blotting, and confocal microscopy. GABAAR protein levels in membrane fractions of TNFα and vehicle-treated subjects were not significantly different by Western Blot, yet high-resolution quantitative confocal imaging revealed that TNFα induces GABAAR trafficking to synapses in a dose-dependent manner by 60 min. TNFα-mediated GABAAR trafficking represents a novel target for CNS excitotoxicity.
url	http://dx.doi.org/10.1155/2012/261345
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Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo

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