Impaired striatal GABA transmission in experimental autoimmune encephalomyelitis

Silvia Rossi, Luca Muzio, Valentina De Chiara, Giorgio Grasselli, Alessandra Musella, Gabriele Musumeci, Georgia Mandolesi, Roberta De Ceglia, Simona Maida, Emilia Biffi, Alessandra Pedrocchi, Andrea Menegon, Giorgio Bernardi, Roberto Furlan, Gianvito Martino, Diego Centonze

Research output: Contribution to journalArticlepeer-review

Abstract

Synaptic dysfunction triggers neuronal damage in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). While excessive glutamate signaling has been reported in the striatum of EAE, it is still uncertain whether GABA synapses are altered. Electrophysiological recordings showed a reduction of spontaneous GABAergic synaptic currents (sIPSCs) recorded from striatal projection neurons of mice with MOG(35-55)-induced EAE. GABAergic sIPSC deficits started in the acute phase of the disease (20-25days post immunization, dpi), and were exacerbated at later time-points (35, 50, 70 and 90dpi). Of note, in slices they were independent of microglial activation and of release of TNF-α. Indeed, sIPSC inhibition likely involved synaptic inputs arising from GABAergic interneurons, because EAE preferentially reduced sIPSCs of high amplitude, and was associated with a selective loss of striatal parvalbumin (PV)-positive GABAergic interneurons, which contact striatal projection neurons in their somatic region, giving rise to more efficient synaptic inhibition. Furthermore, we found also that the chronic persistence of pro-inflammatory cytokines were able, per se, to produce profound alterations of electrophysiological network properties, that were reverted by GABA administration.The results of the present investigation indicate defective GABA transmission in MS models depending from alteration of PV cells number and, in part, deriving from the effects of a chronic inflammation, and suggest that pharmacological agents potentiating GABA signaling might be considered to limit neuronal damage in MS patients.

Original languageEnglish
Pages (from-to)947-956
Number of pages10
JournalBrain, Behavior, and Immunity
Volume25
Issue number5
DOIs
Publication statusPublished - Jul 2011

Keywords

  • EAE
  • Excitotoxicity
  • IPSC
  • MEA
  • Multiple sclerosis
  • Neurodegeneration
  • Parvalbumin
  • Striatum

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

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