title: RANTES correlates with inflammatory activity and synaptic excitability in multiple sclerosis.
abstract: Alterations of synaptic transmission induced by inflammatory activity have been linked to the pathogenic mechanisms of multiple sclerosis (MS). Regulated upon activation, normal T-cell expressed, and secreted (RANTES) is a pro-inflammatory chemokine involved in MS pathophysiology, potentially able to regulate glutamate release and plasticity in MS brains, with relevant consequences on the clinical manifestations of the disease.
  
  
  
  To assess the role of RANTES in the regulation of cortical excitability.
  
  
  
  We explored the association of RANTES levels in the cerebrospinal fluid (CSF) of newly diagnosed MS patients with magnetic resonance imaging (MRI) and laboratory measures of inflammatory activity, as well its role in the control of cortical excitability and plasticity explored by means of transcranial magnetic stimulation (TMS), and in hippocampal mouse slices in vitro.
  
  
  
  CSF levels of RANTES were remarkably high only in active MS patients and were correlated with the concentrations of interleukin-1β. RANTES levels were associated with TMS measures of cortical synaptic excitability, but not with long-term potentiation (LTP)-like plasticity. Similar findings were obtained in mouse hippocampal slices in vitro, where we observed that RANTES enhanced basal excitatory synaptic transmission with no effect on LTP.
  
  
  
  RANTES correlates with inflammation and synaptic excitability in MS brains.
authors.affiliation: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mori
authors.affiliation: Dipartimento di Biologia, Università degli Studi di Roma Tor Vergata, Roma, Italy/Laboratorio di Farmacologia della Plasticità Sinaptica, EBRI-European Brain Research Institute, Roma, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.affiliation: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy/IRCCS Fondazione Santa Lucia, Roma, Italy.
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Nicoletti
authors.affiliation: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy/Clinica di Neurologia, Università Politecnica delle Marche, Ancona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Zagaglia
authors.affiliation: IRCCS Fondazione Santa Lucia, Roma, Italy.
authors.forename: Georgia
authors.initials: G
authors.lastname: Mandolesi
authors.affiliation: Laboratorio di Farmacologia della Plasticità Sinaptica, EBRI-European Brain Research Institute, Roma, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Piccinin
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Finardi
authors.affiliation: Institute of Neurology, Catholic University, Rome, Italy/Brain Connectivity Laboratory, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
authors.affiliation: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
authors.forename: Girolama A
authors.initials: GA
authors.lastname: Marfia
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Multiple Sclerosis Clinical and Research Unit, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy centonze@uniroma2.it.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000328:Adult; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000502:physiology; D016022:Case-Control Studies; D018946:Chemokine CCL5 / Q000134:cerebrospinal fluid*; D000071080:Cortical Excitability; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000134:cerebrospinal fluid; D017774:Long-Term Potentiation; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000276:immunology; D050781:Transcranial Magnetic Stimulation
chemical_list: C483024:CCL5 protein, human; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; C508585:IL1B protein, human; D053583:Interleukin-1beta
keywords: CSF; Chemokines; LTP; TMS; glutamate; synaptic plasticity