title: Dopaminergic dysfunction is associated with IL-1β-dependent mood alterations in experimental autoimmune encephalomyelitis.
abstract: Mood disturbances are frequent in patients with multiple sclerosis (MS), even in non-disabled patients and in the remitting stages of the disease. It is still largely unknown how the pathophysiological process on MS causes anxiety and depression, but the dopaminergic system is likely involved. Aim of the present study was to investigate depressive-like behavior in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, and its possible link to dopaminergic neurotransmission. Behavioral, amperometric and biochemical experiments were performed to determine the role of inflammation in mood control in EAE. First, we assessed the independence of mood alterations from motor disability during the acute phase of the disease, by showing a depressive-like behavior in EAE mice with mild clinical score and preserved motor skills (mild-EAE). Second, we linked such behavioral changes to the selective increased striatal expression of interleukin-1beta (IL-1β) in a context of mild inflammation and to dopaminergic system alterations. Indeed, in the striatum of EAE mice, we observed an impairment of dopamine (DA) neurotransmission, since DA release was reduced and signaling through DA D1- and D2-like receptors was unbalanced. In conclusion, the present study provides first evidence of the link between the depressive-like behavior and the alteration of dopaminergic system in EAE mice, raising the possibility that IL-1β driven dysfunction of dopaminergic signaling might play a role in mood disturbances also in MS patients.
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, 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: 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: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Federici
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Rizzo
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, 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: 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: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: De Vito
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
authors.forename: Nabila
authors.initials: N
authors.lastname: Haji
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Behavioural Neuroscience Laboratory, CEINGE - Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Naples, Italy; Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples (SUN), Caserta, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Usiello
authors.affiliation: 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: Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy; Clinica Neurologica, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy. Electronic address: centonze@uniroma2.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000208:Acute Disease; D000679:Amygdala / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009048:Motor Skills; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012720:Severity of Illness Index; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: C000600618:DRD2 protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine
keywords: Depression; Dopamine; EAE; IL-1β; Striatum