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.

Gentile, A., Fresegna, D., Federici, M., Musella, A., Rizzo, F., Sepman, H., et al. (2015). Dopaminergic dysfunction is associated with IL-1β-dependent mood alterations in experimental autoimmune encephalomyelitis. NEUROBIOLOGY OF DISEASE, 74, 347-358 [10.1016/j.nbd.2014.11.022].

Dopaminergic dysfunction is associated with IL-1β-dependent mood alterations in experimental autoimmune encephalomyelitis

MERCURI, NICOLA BIAGIO;CENTONZE, DIEGO
2015-02-01

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.
feb-2015
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/26 - NEUROLOGIA
English
Con Impact Factor ISI
Depression; Dopamine; EAE; IL-1β; Striatum
This investigation was supported by the Italian National Ministero della Università (Grant No. 2010BN3MXM_007) to DC, by the Italian National Ministero della Salute (Grant No. GR11.148) to AM; by a grant from the European Community (Grant No. 21 4003) (AXREGEN: Axonal regeneration, plasticity & stem cells — Grant agreement 21 4003) and a founding PhD fellowship to NH. DF is supported by a Fondazione Italiana Sclerosi Multipla (FISM) fellowship (No. 2012/B/3). AU is a recipient of NARSAD Independent Investigator Grant 2013 from the Brain & Behavior Research Foundation (Grant No: 20353) and represents Mariano Scippacercola Foundation.
Gentile, A., Fresegna, D., Federici, M., Musella, A., Rizzo, F., Sepman, H., et al. (2015). Dopaminergic dysfunction is associated with IL-1β-dependent mood alterations in experimental autoimmune encephalomyelitis. NEUROBIOLOGY OF DISEASE, 74, 347-358 [10.1016/j.nbd.2014.11.022].
Gentile, A; Fresegna, D; Federici, M; Musella, A; Rizzo, F; Sepman, H; Bullitta, S; De Vito, F; Haji, N; Rossi, S; Mercuri, Nb; Usiello, A; Mandolesi,...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/112498
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