title: Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.
abstract: The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor-α (TNFα). To date, however, no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here, we show that local increase of TNFα in the hippocampal dentate gyrus activates astrocyte TNF receptor type 1 (TNFR1), which in turn triggers an astrocyte-neuron signaling cascade that results in persistent functional modification of hippocampal excitatory synapses. Astrocytic TNFR1 signaling is necessary for the hippocampal synaptic alteration and contextual learning-memory impairment observed in experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis (MS). This process may contribute to the pathogenesis of cognitive disturbances in MS, as well as in other CNS conditions accompanied by inflammatory states or infections.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Samia
authors.initials: S
authors.lastname: Habbas
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Mirko
authors.initials: M
authors.lastname: Santello
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Becker
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Stubbe
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zappia
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Liaudet
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, and Neuroscience Center Zurich, University of Zurich and ETH Zurich, August Forel-Str. 7, 8008 Zurich, Switzerland.
authors.forename: Federica R
authors.initials: FR
authors.lastname: Klaus
authors.affiliation: B.S.R.C. "Alexander Fleming", 34 Fleming Street, 16672 Vari, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Kollias
authors.affiliation: Institute of Experimental Immunology Inflammation and Sickness Behaviour, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, and Neuroscience Center Zurich, University of Zurich and ETH Zurich, August Forel-Str. 7, 8008 Zurich, Switzerland.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Pryce
authors.affiliation: Neuroimmunology and MS Research, University Hospital Zurich, Sternwartestr. 14, 8091 Zurich, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Suter
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland. Electronic address: andrea.volterra@unil.ch.
authors.forename: Andrea
authors.initials: A
authors.lastname: Volterra
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007858:Learning; D008568:Memory; D051379:Mice; D009103:Multiple Sclerosis / Q000503:physiopathology; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; C010739:ifenprodil