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-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.
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Inflammatory cytokines TNF-α and IL-1β play a critical role in chronic neuroinflammatory disorders by modulating the expression and/or properties of synaptic channels.
“inflammatory cytokines, i.e. TNF-α and IL-1β, play a critical role in chronic neuroinflammatory disorders, by modulating the expression and/or properties of synaptic channels”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [12]
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- Authors
- Centonze, D., Muzio, L., Rossi, S., Cavasinni, F., De Chiara, V., Bergami, A., Musella, A., D'Amelio, M., Cavallucci, V., Martorana, A., Bergamaschi, A., Cencioni, M. T., Diamantini, A., Butti, E., Comi, G., Bernardi, G., Cecconi, F., Battistini, L., Furlan, R., & Martino, G.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-03-18
- Volume
- 29
- Issue
- 11
- Pages
- 3442-3452
- ISSN
- 0270-6474
- 1529-2401
- Cited by
- 352
- References
- 4
- Language
- en
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