Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis

Massimiliano Di Filippo, Andrea Mancini, Laura Bellingacci, Lorenzo Gaetani, Petra Mazzocchetti, Teresa Zelante, Livia La Barbera, Antonella De Luca, Michela Tantucci, Alessandro Tozzi, Valentina Durante, Miriam Sciaccaluga, Alfredo Megaro, Davide Chiasserini, Nicola Salvadori, Viviana Lisetti, Emilio Portaccio, Cinzia Costa, Paola Sarchielli, Maria Pia AmatoLucilla Parnetti, Maria Teresa Viscomi, Luigina Romani, Paolo Calabresi

Research output: Contribution to journalArticle

Abstract

Cognitive impairment (CI) is a disabling concomitant of multiple sclerosis (MS) with a complex and controversial pathogenesis. The cytokine interleukin-17A (IL-17A) is involved in the immune pathogenesis of MS, but its possible effects on synaptic function and cognition are still largely unexplored. In this study, we show that the IL-17A receptor (IL-17RA) is highly expressed by hippocampal neurons in the CA1 area and that exposure to IL-17A dose-dependently disrupts hippocampal long-term potentiation (LTP) through the activation of its receptor and p38 mitogen-activated protein kinase (MAPK). During experimental autoimmune encephalomyelitis (EAE), IL-17A overexpression is paralleled by hippocampal LTP dysfunction. An in vivo behavioral analysis shows that visuo-spatial learning abilities are preserved when EAE is induced in mice lacking IL 17A. Overall, this study suggests a key role for the IL-17 axis in the neuro-immune cross-talk occurring in the hippocampal CA1 area and its potential involvement in synaptic dysfunction and MS-related CI.
Original languageEnglish
Pages (from-to)N/A-N/A
JournalCell Reports
Volume37
DOIs
Publication statusPublished - 2021

Keywords

  • cognitive impairment
  • experimental autoimmune encephalomyelitis
  • hippocampus
  • inflammation
  • interleukin-17
  • multiple sclerosis
  • neuroimmunology
  • synaptic plasticity

Fingerprint

Dive into the research topics of 'Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis'. Together they form a unique fingerprint.

Cite this