title: Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system.
abstract: Increasing attention is being paid to the role of inflammatory and immune molecules in the modulation of central nervous system (CNS) function. Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, the receptors for which are expressed on neurones and glial cells throughout the CNS. Through the action of its two receptors, it has a broad range of actions on neurones which may be either neuroprotective or neurotoxic. It plays a facilitatory role in glutamate excitotoxicity, both directly and indirectly by inhibiting glial glutamate transporters on astrocytes. Additionally, TNF-alpha has direct effects on glutamate transmission, for example increasing expression of AMPA receptors on synapses. TNF-alpha also plays a role in synaptic plasticity, inhibiting long-term potentiation (LTP), a process dependent on p38 mitogen activated kinase (p38 MAP) kinase. In the following review we look at these and other effects of TNF-alpha in the CNS.
authors.affiliation: Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Pickering
authors.forename: Derval
authors.initials: D
authors.lastname: Cumiskey
authors.forename: John J
authors.initials: JJ
authors.lastname: O'Connor
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000166:cytology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D048051:p38 Mitogen-Activated Protein Kinases