title: Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis.
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-alpha 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.
authors.affiliation: Neurologic Clinic, Department of Neuroscience, Tor Vergata University, 00133 Rome, Italy. centonze@uniroma2.it
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Francesca
authors.initials: F
authors.lastname: Cavasinni
authors.forename: Valentina
authors.initials: V
authors.lastname: De Chiara
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.forename: Marcello
authors.initials: M
authors.lastname: D'Amelio
authors.forename: Virve
authors.initials: V
authors.lastname: Cavallucci
authors.forename: Alessandro
authors.initials: A
authors.lastname: Martorana
authors.forename: Andrea
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cencioni
authors.forename: Adamo
authors.initials: A
authors.lastname: Diamantini
authors.forename: Erica
authors.initials: E
authors.lastname: Butti
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Cecconi
authors.forename: Luca
authors.initials: L
authors.lastname: Battistini
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D018091:Receptors, AMPA