title: Oral fingolimod rescues the functional deficits of synapses in experimental autoimmune encephalomyelitis.
abstract: BACKGROUND AND PURPOSE Alterations of glutamate-mediated synaptic transmission occur early during neuroinflammatory insults, and lead to degenerative neuronal damage in multiple sclerosis (MS) and also in experimental autoimmune encephalomyelitis (EAE), which is a murine model of MS. Fingolimod is an effective orally active agent for the treatment of MS, affecting lymphocyte invasion of the brain. However, it is still unclear if fingolimod can be neuroprotective in this disorder. EXPERIMENTAL APPROACH Using neurophysiological recordings and morphological evaluation of dendritic integrity, we evaluated the effects of oral fingolimod on the clinical score of EAE mice in order to determine whether the compound was associated with preservation of synaptic transmission. KEY RESULTS Oral fingolimod prevented and reversed the pre- and postsynaptic alterations of glutamate transmission in EAE mice. These effects were associated with a clear amelioration of the clinical deterioration seen in EAE mice, and with a significant inhibition of neuronal dendritic pathology. Fingolimod did not alter the spontaneous excitatory postsynaptic currents in control animals, suggesting that only the pathological processes behind the inflammation-induced defects in glutamate transmission were modulated by this compound. CONCLUSIONS AND IMPLICATIONS The beneficial effects of fingolimod on the clinical, synaptic and dendritic abnormalities of murine EAE might correlate with the neuroprotective actions of this agent, as observed in MS patients. LINKED ARTICLE This article is commented on by Gillingwater, pp. 858-860 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01612.x.
authors: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
authors: S
authors: S
authors: Rossi
authors: T
authors: T
authors: Lo Giudice
authors: V
authors: V
authors: De Chiara
authors: A
authors: A
authors: Musella
authors: V
authors: V
authors: Studer
authors: C
authors: C
authors: Motta
authors: G
authors: G
authors: Bernardi
authors: G
authors: G
authors: Martino
authors: R
authors: R
authors: Furlan
authors: A
authors: A
authors: Martorana
authors: D
authors: D
authors: Centonze
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride; D018698:Glutamic Acid / Q000502:physiology; D006023:Glycoproteins; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D006023:Glycoproteins; D007166:Immunosuppressive Agents; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011409:Propylene Glycols; C445081:myelin oligodendrocyte glycoprotein (35-55); D018698:Glutamic Acid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine