Format

Send to

Choose Destination
Cell. 2015 Dec 17;163(7):1730-41. doi: 10.1016/j.cell.2015.11.023. Epub 2015 Dec 10.

Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.

Author information

1
Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.
2
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.
3
B.S.R.C. "Alexander Fleming", 34 Fleming Street, 16672 Vari, Greece.
4
Institute of Experimental Immunology Inflammation and Sickness Behaviour, University of Zurich, Winterthurerstr. 190, 8057 Zurich, Switzerland.
5
Neuroimmunology and MS Research, University Hospital Zurich, Sternwartestr. 14, 8091 Zurich, Switzerland.
6
Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland. Electronic address: andrea.volterra@unil.ch.

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.

PMID:
26686654
DOI:
10.1016/j.cell.2015.11.023
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center