Cell Reports
Volume 37, Issue 10, 7 December 2021, 110094
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Article
Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis

https://doi.org/10.1016/j.celrep.2021.110094Get rights and content
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Highlights

  • Hippocampal neurons express IL-17RA both under control conditions and during EAE

  • IL-17A dose-dependently blocks LTP via the activation of IL-17RA and p38 MAPK

  • Hippocampal IL-17A overexpression and synaptic dysfunction both occur during EAE

  • The lack of IL-17A ameliorates EAE-related cognitive deficits

Summary

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

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

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

10

These authors contributed equally

11

Lead contact