Livia La Barbera (Italy)
University Campus-Biomedico, Rome, Italy Unit of Molecular Neurosciences, Department of MedicineAuthor Of 1 Presentation
INTERLEUKIN-17 AXIS IN THE MODULATION OF CORTICAL AND SUBCORTICAL SYNAPTIC PLASTICITY ACROSS DISEASE STAGES IN EXPERIMENTAL MULTIPLE SCLEROSIS
- Andrea Mancini (Italy)
Abstract
Background and Aims:
Interleukin-17A (IL-17) is known to be deeply involved in the immunopathogenesis of multiple sclerosis (MS), but recent reports suggest that it may also participate in synaptic modulation. The aim of our study was to explore the role exerted by IL-17 axis in the regulation of hippocampal and striatal synaptic plasticity in physiological conditions and across different stages of experimental MS.
Methods:
Electrophysiological recordings were performed in the hippocampus (CA1 area) and in the striatum of control mice, mice affected by experimental autoimmune encephalomyelitis (EAE) and mice lacking IL-17 or IL-17 receptor (IL-17R). IL-17 levels were assessed through ELISA assays and IL-17 and IL-17R expression patterns through immunohistochemical analysis.
Results:
Functional IL-17 axis is required for physiological hippocampal and striatal synaptic plasticity, since the absence of IL-17R and the exposure to high IL-17 levels were associated with altered LTP induction. Hippocampal long-term potentiation (LTP) was disrupted during pre-acute and acute EAE phases, in parallel with increased IL-17 hippocampal expression levels. The recovery phase of EAE was characterized by a restoration of hippocampal LTP and by a reduction of IL-17 production. Hippocampal-dependent cognitive tasks are preserved when EAE is induced in mice lacking IL-17. Immunohistochemical analysis suggested that microglial-produced IL-17 may directly act on IL-17Rs expressed by hippocampal neurons. The inhibition of IL-17R axis (p38MAPK) or the in vitro exposure to anti-IL-17 antibodies limited the IL-17-dependent disruption of hippocampal LTP.
Conclusions:
Targeting IL-17 axis may help counteract the loss of brain plastic properties contributing to disease progression and cognitive impairment during MS.