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

• DOI: 10.1016/j.celrep.2021.110094
• Publication Date: 2021-12-08T01:59:20Z
• Authors: Massimiliano Di F...; 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 Amato; Lucilla Parnetti; Maria Teresa Viscomi; Luigina Romani; Paolo Calabresi
• Keywords: Pathogenesis; Hippocampal sclerosis

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