TY - JOUR T1 - Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3442 LP - 3452 DO - 10.1523/JNEUROSCI.5804-08.2009 VL - 29 IS - 11 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 Y1 - 2009/03/18 UR - http://www.jneurosci.org/content/29/11/3442.abstract N2 - 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. ER -