title: Cladribine interferes with IL-1β synaptic effects in experimental multiple sclerosis.
abstract: Alterations of glutamate-mediated synaptic transmission occur in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Here we investigated whether intracerebroventricular (Icv) administration of cladribine has effects on EAE. Icv infusion of cladribine reduced the clinical deficits of EAE mice and reversed EAE-induced enhancement of excitatory postsynaptic current (sEPSC) frequency, a neurophysiological measure of glutamatergic synaptopathy associated with central inflammation. Cladribine failed to interfere with EAE-induced microglial and astroglial activation, but blocked EAE synaptic alterations by interfering with interleukin-1β effects. Cladribine possesses neuroprotective properties in experimental MS that are independent of its peripheral immunosuppressant action.
authors.affiliation: Fondazione Santa Lucia, Centro Europeo per la Ricerca sul Cervello (CERC), 00143 Rome, Italy; UOC Neurologia, Dipartimento di Medicina dei Sistemi, Università Tor Vergata, 00133 Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Musella
authors.forename: Georgia
authors.initials: G
authors.lastname: Mandolesi
authors.forename: Antonietta
authors.initials: A
authors.lastname: Gentile
authors.forename: Silvia
authors.initials: S
authors.lastname: Rossi
authors.forename: Valeria
authors.initials: V
authors.lastname: Studer
authors.forename: Caterina
authors.initials: C
authors.lastname: Motta
authors.forename: Helena
authors.initials: H
authors.lastname: Sepman
authors.forename: Diego
authors.initials: D
authors.lastname: Fresegna
authors.forename: Nabila
authors.initials: N
authors.lastname: Haji
authors.forename: Andrea
authors.initials: A
authors.lastname: Paolillo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D002614:Chelating Agents / Q000494:pharmacology; D017338:Cladribine / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000166:cytology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects*
chemical_list: D002614:Chelating Agents; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D018698:Glutamic Acid; D017338:Cladribine; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
keywords: Cladribine; EAE; EPSC; IL-1β; Microglia; Striatum