1. Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling
- Author
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Nicolas Liaudet, Giovanna Zappia, George Kollias, Federica Klaus, Denise Becker, Samia Habbas, Andrea Volterra, Christopher R. Pryce, Tobias Suter, Hiltrud Stubbe, Adriano Fontana, Mirko Santello, University of Zurich, and Volterra, Andrea
- Subjects
medicine.medical_treatment ,Hippocampal formation ,Astrocytes/metabolism ,Mice ,0302 clinical medicine ,Piperidines ,Receptors, Tumor Necrosis Factor, Type I/metabolism ,Dentate Gyrus/metabolism ,Multiple Sclerosis/physiopathology ,610 Medicine & health ,Tumor Necrosis Factor-alpha/metabolism ,0303 health sciences ,Cytokine ,medicine.anatomical_structure ,Animals ,Encephalomyelitis, Autoimmune, Experimental/immunology ,Encephalomyelitis, Autoimmune, Experimental/physiopathology ,Humans ,Learning ,Memory ,Receptors, N-Methyl-D-Aspartate/metabolism ,Signal Transduction ,Receptors, Tumor Necrosis Factor, Type I ,Tumor necrosis factor alpha ,Signal transduction ,Astrocyte ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Genetics and Molecular Biology ,Biology ,Receptors, N-Methyl-D-Aspartate ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,030304 developmental biology ,Autoimmune encephalitis ,Tumor Necrosis Factor-alpha ,Biochemistry, Genetics and Molecular Biology(all) ,Dentate gyrus ,Multiple sclerosis ,medicine.disease ,Astrocytes ,10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics ,Dentate Gyrus ,General Biochemistry ,Immunology ,030217 neurology & neurosurgery - Abstract
© 2015 Elsevier Inc. All rights reserved. The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor a (TNFa). To date however no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here we show that local increase of TNFa 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.
- Published
- 2015
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