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Publication : Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.

First Author  Habbas S Year  2015
Journal  Cell Volume  163
Issue  7 Pages  1730-41
PubMed ID  26686654 Mgi Jnum  J:227981
Mgi Id  MGI:5704227 Doi  10.1016/j.cell.2015.11.023
Citation  Habbas S, et al. (2015) Neuroinflammatory TNFalpha Impairs Memory via Astrocyte Signaling. Cell 163(7):1730-41
abstractText  The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor-alpha (TNFalpha). To date, however, no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here, we show that local increase of TNFalpha 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.
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