title: TNFα in synaptic function: switching gears.
abstract: Pathological brain states are known to induce massive production of proinflammatory cytokines, including tumor necrosis factor alpha (TNFα). At much lower levels, these cytokines are also present in the healthy brain, where it is increasingly being recognized that they exert regulatory influences. Recent studies suggest that TNFα plays important roles in controlling synaptic transmission and plasticity. Here, we discuss the evidence in support of synaptic regulation by TNFα and the underlying cellular mechanisms, including control of AMPA receptor trafficking and glutamate release from astrocytes. These findings suggest that increases in TNFα levels (caused by nervous system infection, injury, or disease) transform the physiological actions of the cytokine into deleterious ones. This functional switch may contribute to cognitive alterations in several brain pathologies.
authors: Department of Cell Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors: Mirko
authors: M
authors: Santello
authors: Andrea
authors: A
authors: Volterra
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology*; D002493:Central Nervous System Diseases / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid