title: Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis.
abstract: Multiple sclerosis (MS) has long been regarded as a chronic inflammatory disease of the white matter that leads to demyelination and eventually to neurodegeneration. In the past decade, several aspects of MS pathogenesis have been challenged, and degenerative changes of the grey matter, which are independent of demyelination, have become a topic of interest. CNS inflammation in MS and experimental autoimmune encephalomyelitis (EAE; a disease model used to study MS in rodents) causes a marked imbalance between GABAergic and glutamatergic transmission, and a loss of synapses, all of which leads to a diffuse 'synaptopathy'. Altered synaptic transmission can occur early in MS and EAE, independently of demyelination and axonal loss, and subsequently causes excitotoxic damage. Inflammation-driven synaptic abnormalities are emerging as a prominent pathogenic mechanism in MS-importantly, they are potentially reversible and, therefore, represent attractive therapeutic targets. In this Review, we focus on the connection between inflammation and synaptopathy in MS and EAE, which sheds light not only on the pathophysiology of MS but also on that of primary neurodegenerative disorders in which inflammatory processes contribute to disease progression.
authors.affiliation: IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Georgia
authors.initials: G
authors.lastname: Mandolesi
authors.affiliation: Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Gentile
authors.affiliation: IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.affiliation: IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Fresegna
authors.affiliation: Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Vito
authors.affiliation: IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bullitta
authors.affiliation: IRCCS Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.|Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Helena
authors.initials: H
authors.lastname: Sepman
authors.affiliation: Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Girolama A
authors.initials: GA
authors.lastname: Marfia
authors.affiliation: IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Via Atinense 18, 86077 Pozzilli, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000818:Animals; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology*; D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications*; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology*; D013569:Synapses / Q000473:pathology*