PT  - JOURNAL ARTICLE
AU  - Diego Centonze
AU  - Luca Muzio
AU  - Silvia Rossi
AU  - Francesca Cavasinni
AU  - Valentina De Chiara
AU  - Alessandra Bergami
AU  - Alessandra Musella
AU  - Marcello D'Amelio
AU  - Virve Cavallucci
AU  - Alessandro Martorana
AU  - Andrea Bergamaschi
AU  - Maria Teresa Cencioni
AU  - Adamo Diamantini
AU  - Erica Butti
AU  - Giancarlo Comi
AU  - Giorgio Bernardi
AU  - Francesco Cecconi
AU  - Luca Battistini
AU  - Roberto Furlan
AU  - Gianvito Martino
TI  - Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis
AID  - 10.1523/JNEUROSCI.5804-08.2009
DP  - 2009 Mar 18
TA  - The Journal of Neuroscience
PG  - 3442--3452
VI  - 29
IP  - 11
4099  - http://www.jneurosci.org/content/29/11/3442.short
4100  - http://www.jneurosci.org/content/29/11/3442.full
SO  - J. Neurosci.2009 Mar 18; 29
AB  - 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.