title: The link between inflammation, synaptic transmission and neurodegeneration in multiple sclerosis.
abstract: Multiple sclerosis (MS) has been classically regarded as a disorder of the white matter of the central nervous system (CNS). However, early alterations of the neuronal compartment occurring in this disorder are partially independent of demyelination. Soluble inflammatory cytokines and glutamate have been proposed as major determinants of neurodegeneration in MS as well as in its experimental animal model, namely experimental autoimmune encephalomyelitis (EAE). The relationship between these two major determinants has been largely elusive. In recent years, unexpected connections have emerged between immune cells and soluble cytokines on the one hand, and synaptic transmission and neurodegeneration on the other. Neurophysiological recordings have recently shown that glutamate-mediated excitatory postsynaptic currents are enhanced during the early phase of EAE, because of altered expression and phosphorylation of AMPA receptors and the downregulation of the immediate early gene Arc/Arg3.1. The synaptic alterations occurring during neuroinflammatory diseases are largely mediated by inflammatory cytokines released from infiltrating T cells and from activated microglia, and are responsible, at least in part, for irreversible dendritic pathology. Collectively, the data covered in this review article suggest that CNS-confined inflammation in MS is associated with the release of soluble molecules, which are capable of altering excitatory synaptic transmission and, finally, of stimulating secondary neurodegenerative gray matter pathology.
authors.affiliation: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy. centonze@uniroma2.it
authors.forename: D
authors.initials: D
authors.lastname: Centonze
authors.forename: L
authors.initials: L
authors.lastname: Muzio
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.forename: R
authors.initials: R
authors.lastname: Furlan
authors.forename: G
authors.initials: G
authors.lastname: Bernardi
authors.forename: G
authors.initials: G
authors.lastname: Martino
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology; D007249:Inflammation / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D009410:Nerve Degeneration / Q000276:immunology*; D009435:Synaptic Transmission
chemical_list: D016207:Cytokines; D018698:Glutamic Acid