Tumor Necrosis Factor Alpha Mediates GABAA Receptor Trafficking to the Plasma Membrane of Spinal Cord Neurons In Vivo. (12th March 2012)

• Record Type: Journal Article
• Authors: Stück, Ellen D.; Christensen, Randolph N.; Huie, J. Russell; Tovar, C. Amy; Miller, Brandon A.; Nout, Yvette S.; Bresnahan, Jacqueline C.; Beattie, Michael S.; Ferguson, Adam R.
• Other Names: Ivanco Tammy Academic Editor.
• Is Part Of: Neural plasticity. Volume 2012(2012)
• Publication Date: 2012-03-12
• Subjects: Neuroplasticity -- Periodicals; 612.82
• DOI: 10.1155/2012/261345
• Languages: English
• ISSNs: 2090-5904

Abstract

Abstract : The proinflammatory cytokine TNF α contributes to cell death in central nervous system (CNS) disorders by altering synaptic neurotransmission. TNF α 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 TNF α exposure is associated with a rapid internalization of GABAA receptors (GABAA Rs), suggesting complex timing and dose dependency of the CNS's response to TNF α . However, the effect of TNF α on GABAA R trafficking in vivo remains unclear. We assessed the effect of TNF α nanoinjection on rapid GABAA R changes in rats (N = 30 ) using subcellular fractionation, quantitative western blotting, and confocal microscopy. GABAA R protein levels in membrane fractions of TNF α and vehicle-treated subjects were not significantly different by Western Blot, yet high-resolution quantitative confocal imaging revealed that TNF α induces GABAA R trafficking to synapses in a dose-dependent manner by 60 min. TNF α -mediated GABAA R trafficking represents a novel target for CNS excitotoxicity.