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Irish Journal of Medical Science

, Volume 182, Issue 2, pp 157–162 | Cite as

Targeting tumour necrosis factor-α in hypoxia and synaptic signalling

  • J. J. O’Connor
Review Article

Abstract

Tumour necrosis factor (TNF)-α is a pro-inflammatory cytokine, which is synthesised and released in the brain by astrocytes, microglia and neurons in response to numerous internal and external stimuli. It is involved in many physiological and pathophysiological processes such as gene transcription, cell proliferation, apoptosis, synaptic signalling and neuroprotection. The complex actions of TNF-α in the brain are under intense investigation. TNF-α has the ability to induce selective necrosis of some cells whilst sparing others and this has led researchers to discover multiple activated signalling cascades. In many human diseases including acute stroke and inflammation and those involving hypoxia, levels of TNF-α are increased throughout different brain regions. TNF-α signalling may also have several positive and negative effects on neuronal function including glutamatergic synaptic transmission and plasticity. Exogenous TNF-α may also exacerbate the neuronal response to hypoxia. This review will summarise the actions of TNF-α in the central nervous system on synaptic signalling and its effects during hypoxia.

Keywords

TNF-α Hypoxia Prolyl hydroxylase Hippocampus Synaptic transmission Synaptic plasticity Inflammation 

Notes

Acknowledgments

I would like to thank Gatambwa Mukandala for help with the production of the figures. This work was supported in part by funding from Science Foundation Ireland (SFI; 09/RFP/NES2450).

Conflict of interest

None.

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Copyright information

© Royal Academy of Medicine in Ireland 2013

Authors and Affiliations

  1. 1.UCD School of Biomolecular and Biomedical ScienceConway Institute of Biomolecular and Biomedical Research, University College Dublin, BelfieldDublin 4Ireland

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