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- Title
Inflammation Triggers Synaptic Alteration and Degeneration in Experimental Autoimmune Encephalomyelitis.
- Authors
Centonze, Diego; Muzio, Luca; Rossi, Silvia; Cavasinni, Francesca; De Chiara, Valentina; Bergami, Alessandra; Musella, Alessandra; D'Amelio, Marcello; Cavallucci, Virve; Martorana, Alessandro; Bergamaschi, Andrea; Cencioni, Maria Teresa; Diamantini, Adamo; Butti, Erica; Comi, Giancarlo; Bernardi, Giorgio; Cecconi, Francesco; Battistini, Luca; Furlan, Roberto; Martino, Gianvito
- 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.
- Subjects
CENTRAL nervous system diseases; ENCEPHALOMYELITIS; TUMOR necrosis factors; CYTOKINES; VIRUS diseases
- Publication
Journal of Neuroscience, 2009, Vol 29, Issue 11, p3442
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.5804-08.2009