Tumor necrosis factor-α potentiates long-term potentiation in the rat dentate gyrus after acute hypoxia

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Title: Tumor necrosis factor-α potentiates long-term potentiation in the rat dentate gyrus after acute hypoxia
Authors: Wall, Audrey M.
Mukandala, Gatambwa
Greig, Nigel H.
O'Connor, J. J.
Permanent link: http://hdl.handle.net/10197/6355
Date: 12-Jan-2015
Abstract: An inadequate supply of oxygen in the brain may lead to an inflammatory response through neuronal and glial cells that can result in neuronal damage. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that is released during acute hypoxia and can have neurotoxic or neuroprotective effects in the brain. Both TNF-α and interleukin-1β (IL-1β) have been shown by a number of research groups to alter synaptic scaling and also to inhibit long-term potentiation (LTP) in the hippocampus when induced by specific high-frequency stimulation (HFS) protocols. This study examines the effects of TNF-α on synaptic transmission and plasticity in hippocampal slices after acute hypoxia using two HFS protocols. Field excitatory postsynaptic potentials were elicited in the medial perforant pathway of the dentate gyrus. Exogenous TNF-α (5 ng/ml) attenuated LTP induced by theta burst stimulation but had no effect on LTP induced by a more prolonged HFS. Pretreatment with lipopolysaccharide (100 ng/ml) or TNF-α but not IL-1β (4 ng/ml) prior to a 30-min hypoxic insult resulted in a significant enhancement of LTP post hypoxia when induced by the HFS. Anti-TNF, 3,6′-dithiothalidomide (a TNF-α synthesis inhibitor), and SB203580 (a p38 MAPK inhibitor) significantly reduced this effect. These results indicate an important modulatory role for elevated TNF-α levels on LTP in the hippocampus after an acute hypoxic event.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: Wiley
Journal: Journal of Neuroscience Research
Volume: 93
Issue: 5
Start page: 815
End page: 829
Copyright (published version): 2015 Wiley Periodicals, Inc.
Keywords: Tumor necrosis factor-αInterleukin-1βLong-term potentiationDentate gyrusHypoxiaHigh-frequency stimulationTheta burst stimulation3,6′-dithiothalidomide1,6′-dithiorevlimidCNTO1081Prolyl hydroxylase inhibition
DOI: 10.1002/jnr.23540
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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