title: Inflammation inhibits GABA transmission in multiple sclerosis.
abstract: Abnormal glutamate-dependent synaptic excitation contributes to neuronal damage in multiple sclerosis (MS). Little is known about the involvement of the GABA system in this disorder. Here we found that cerebrospinal fluid (CSF) from MS patients with enhanced brain lesions on magnetic resonance imaging inhibited GABA transmission in mouse brain slices. Enhanced IL-1β neuronal action was responsible for this effect, because IL-1β receptor antagonist blocked, and exogenous IL-1β mimicked the synaptic effect of inflamed CSF. Our results provide evidence that focal inflammation in MS perturbs the cytokine milieu within the circulating CSF, resulting in diffuse GABAergic alteration in neurons.
authors.affiliation: Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy.
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: Valentina
authors.initials: V
authors.lastname: De Chiara
authors.forename: Francesca
authors.initials: F
authors.lastname: Barbieri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000134:cerebrospinal fluid / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials; D053583:Interleukin-1beta / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D005680:gamma-Aminobutyric Acid