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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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2012/261345 |
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| 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 |
| 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 |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-89292cf6a78a4e80929822a2116e10ed |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-89292cf6a78a4e80929822a2116e10ed2025-02-03T05:44:22ZengWileyNeural 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 |
| 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 |
| title | 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_short | 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 |
| url | http://dx.doi.org/10.1155/2012/261345 |
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