Lorenzo Gaetani (Italy)
University of Perugia Department of Medicine and SurgeryAuthor Of 2 Presentations
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.
A CSF BIOMARKER OF INTRATHECAL B CELLS ACTIVATION CORRELATES WITH MEMORY IMPAIRMENT IN MULTIPLE SCLEROSIS
- Lorenzo Gaetani (Italy)
Abstract
Background and Aims:
Cognitive impairment (CI) is a common clinical feature of multiple sclerosis (MS), but its pathophysiology is only partially known. Cerebrospinal fluid (CSF) biomarkers, by reflecting the ongoing pathology, may help in better understanding the determinants of CI in MS. Kappa free light chain index (k-index) is a sensitive biomarker of intrathecal B cells activation. Herein, we investigated the association between k-index and cognitive performance in MS patients.
Methods:
We selected for the study relapsing MS patients who, at the time of the diagnostic work-up, underwent CSF analysis and a complete neuropsychological assessment with the Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRBN). k-index was assessed by nephelometry in a Siemens™ BN II automated analyser using N latex FLC kappa assay for CSF and serum samples (Siemens Healthcare Diagnostics).
Results:
Thirty-nine patients (F:M 2.9, mean age 39.3±13.1 years) were included in the study. k-index was not significantly different between patients with and without global CI and spatial memory, information processing speed and verbal fluency impairment. On the contrary, k-index was higher in patients with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p<0.05). k-index was negatively associated with Selective Reminding Test (SRT) scores and explained up to 32% of their variance (SRT-LTS: r =-0.6, p<0.001; R2=0.32, F(1.37)=17.2, p<0.001; SRT-CLTR: r=-0.5, p<0.01; R2=0.22, F(1.4)=10.5, p<0.01; SRT-DR: r=-0.4, p<0.05; R2=0.16, F(1.4)=6.7, p<0.05) (Figure).
Conclusions:
k-index is higher in MS patients with impaired verbal memory. Intrathecal B cells activation may be associated with memory dysfunction in MS through mechanisms that deserve further investigations.
Presenter of 1 Presentation
A CSF BIOMARKER OF INTRATHECAL B CELLS ACTIVATION CORRELATES WITH MEMORY IMPAIRMENT IN MULTIPLE SCLEROSIS
- Lorenzo Gaetani (Italy)
Abstract
Background and Aims:
Cognitive impairment (CI) is a common clinical feature of multiple sclerosis (MS), but its pathophysiology is only partially known. Cerebrospinal fluid (CSF) biomarkers, by reflecting the ongoing pathology, may help in better understanding the determinants of CI in MS. Kappa free light chain index (k-index) is a sensitive biomarker of intrathecal B cells activation. Herein, we investigated the association between k-index and cognitive performance in MS patients.
Methods:
We selected for the study relapsing MS patients who, at the time of the diagnostic work-up, underwent CSF analysis and a complete neuropsychological assessment with the Rao’s Brief Repeatable Battery of Neuropsychological Tests (BRBN). k-index was assessed by nephelometry in a Siemens™ BN II automated analyser using N latex FLC kappa assay for CSF and serum samples (Siemens Healthcare Diagnostics).
Results:
Thirty-nine patients (F:M 2.9, mean age 39.3±13.1 years) were included in the study. k-index was not significantly different between patients with and without global CI and spatial memory, information processing speed and verbal fluency impairment. On the contrary, k-index was higher in patients with verbal memory impairment (median 99.6, range 58.5-195.2 vs. median 37.2, range 2.3-396.9, p<0.05). k-index was negatively associated with Selective Reminding Test (SRT) scores and explained up to 32% of their variance (SRT-LTS: r =-0.6, p<0.001; R2=0.32, F(1.37)=17.2, p<0.001; SRT-CLTR: r=-0.5, p<0.01; R2=0.22, F(1.4)=10.5, p<0.01; SRT-DR: r=-0.4, p<0.05; R2=0.16, F(1.4)=6.7, p<0.05) (Figure).
Conclusions:
k-index is higher in MS patients with impaired verbal memory. Intrathecal B cells activation may be associated with memory dysfunction in MS through mechanisms that deserve further investigations.