title: The interplay between inflammatory cytokines and the endocannabinoid system in the regulation of synaptic transmission.
abstract: Excessive glutamate-mediated synaptic transmission and secondary excitotoxicity have been proposed as key determinants of neurodegeneration in many neurological diseases. Soluble mediators of inflammation have recently gained attention owing to their ability to enhance glutamate transmission and affect synaptic sensitivity to neurotransmitters. In the complex crosstalk between soluble immunoactive molecules and synapses, the endocannabinoid system (ECS) plays a central role, exerting an indirect neuroprotective action by inhibiting cytokine-dependent synaptic alterations, and a direct neuroprotective effect by limiting glutamate transmission and excitotoxic damage. On the other hand, the endocannabinoid (eCB)-mediated control of synaptic transmission is altered by proinflammatory cytokines with consequent effects in central nervous system (CNS) disorders. In this review, we summarize the interactions, at the pre- and postsynaptic level, between major inflammatory cytokines and the ECS. In addition, the behavioral and clinical consequences of the modulation of synaptic transmission during neuroinflammation are discussed. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'.
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy; Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy; Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Motta
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy; Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.affiliation: Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy; Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy. Electronic address: centonze@uniroma2.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000378:metabolism / Q000503:physiopathology; D063388:Endocannabinoids / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D009103:Multiple Sclerosis / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission
chemical_list: D016207:Cytokines; D063388:Endocannabinoids; D018836:Inflammation Mediators
keywords: CB1 receptor; GABA; Glutamate; IL-1β; Multiple sclerosis; TNF; TRPV1