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

Cell Rep. 2021 Dec 7;37(10):110094. doi: 10.1016/j.celrep.2021.110094.

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.

Keywords: cognitive impairment; experimental autoimmune encephalomyelitis; hippocampus; inflammation; interleukin-17; multiple sclerosis; neuroimmunology; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • CA1 Region, Hippocampal / metabolism*
  • CA1 Region, Hippocampal / pathology
  • CA1 Region, Hippocampal / physiopathology
  • Cognition*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Encephalomyelitis, Autoimmune, Experimental / psychology
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Long-Term Potentiation
  • Male
  • Mice, Biozzi
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity*
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism*
  • Signal Transduction
  • Spatial Learning
  • Synapses / metabolism*
  • Synapses / pathology
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Il17a protein, mouse
  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin-17
  • p38 Mitogen-Activated Protein Kinases