Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis

Diego Centonze, Luca Muzio, Silvia Rossi, Francesca Cavasinni, Valentina De Chiara, Alessandra Bergami, Alessandra Musella, Marcello D'Amelio, Virve Cavallucci, Alessandro Martorana, Andrea Bergamaschi, Maria Teresa Cencioni, Adamo Diamantini, Erica Butti, Giancarlo Comi, Giorgio Bernardi, Francesco Cecconi, Luca Battistini, Roberto Furlan, Gianvito Martino

Research output: Contribution to journalArticle

Abstract

Neurodegeneration is the irremediable pathological event occurring during chronic inflammatory diseases of the CNS. Here we show that, in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, inflammation is capable in enhancing glutamate transmission in the striatum and in promoting synaptic degeneration and dendritic spine loss. These alterations occur early in the disease course, are independent of demyelination, and are strongly associated with massive release of tumor necrosis factor-α from activated microglia. CNS invasion by myelin-specific blood-borne immune cells is the triggering event, and the downregulation of the early gene Arc/Arg3.1, leading to the abnormal expression and phosphorylation of AMPA receptors, represents a culminating step in this cascade of neurodegenerative events. Accordingly, EAE-induced synaptopathy subsided during pharmacological blockade of AMPA receptors. Our data establish a link between neuroinflammation and synaptic degeneration and calls for early neuroprotective therapies in chronic inflammatory diseases of the CNS.

Original languageEnglish
Pages (from-to)3442-3452
Number of pages11
JournalJournal of Neuroscience
Volume29
Issue number11
DOIs
Publication statusPublished - Mar 18 2009

ASJC Scopus subject areas

  • Neuroscience(all)

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