Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system.
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.
Pickering
Mark
M
Department of Human Anatomy and Physiology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Cumiskey
Derval
D
O'Connor
John J
JJ
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
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D048051:p38 Mitogen-Activated Protein Kinases