Synovial fluid-derived extracellular vesicles of patients with arthritides contribute to hippocampal synaptic dysfunctions and increase with mood disorders severity in humans

Cambria, C. et al. (2022) Synovial fluid-derived extracellular vesicles of patients with arthritides contribute to hippocampal synaptic dysfunctions and increase with mood disorders severity in humans. Cells, 11(15), 2276. (doi: 10.3390/cells11152276) (PMID:35892573) (PMCID:PMC9331474)

Abstract

Arthritides are a highly heterogeneous group of disorders that include two major clinical entities, localized joint disorders such as osteoarthritis (OA) and systemic autoimmune-driven diseases such as rheumatoid arthritis (RA). Arthritides are characterized by chronic debilitating musculoskeletal conditions and systemic chronic inflammation. Poor mental health is also one of the most common comorbidities of arthritides. Depressive symptoms which are most prevalent, negatively impact patient global assessment diminishing the probability of achieving the target of clinical remission. Here, we investigated new insights into mechanisms that link different joint disorders to poor mental health, and to this issue, we explored the action of the synovial fluid-derived extracellular vesicles (EVs) on neuronal function. Our data show that the exposure of neurons to different concentrations of EVs derived from both RA and OA synovial fluids (RA-EVs and OA-EVs) leads to increased excitatory synaptic transmission but acts on specific modifications on excitatory or inhibitory synapses, as evidenced by electrophysiological and confocal experiments carried out in hippocampal cultures. The treatment of neurons with EVs membrane is also responsible for generating similar effects to those found with intact EVs suggesting that changes in neuronal ability arise upon EVs membrane molecules′ interactions with neurons. In humans with arthritides, we found that nearly half of patients (37.5%) showed clinically significant psychiatric symptoms (CGIs score ≥ 3), and at least mild anxiety (HAM-A ≥ 7) or depression (MADRS and HAM-D ≥ 7); interestingly, these individuals revealed an increased concentration of synovial EVs. In conclusion, our data showing opposite changes at the excitatory and inhibitory levels in neurons treated with OA- and RA-EVs, lay the scientific basis for personalized medicine in OA and RA patients, and identify EVs as new potential actionable biomarkers in patients with OA/RA with poor mental health.

• Item Type: Articles
• Additional Information: Funding: F.A. is economically supported by the Italian Ministry of University and Research, PRIN 2017-“Progetti di Ricerca di Rilevante Interesse Nazionale”-(5C22WM to FA). F.A., M.B., F.I. are economically supported by SEED 2019–“Bando Straordinario per Progetti Interdipartimentali”, UNIMI. The authors acknowledge the support of the APC central fund of the University of Milan.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Coletto, Ms Lavinia
• Authors: Cambria, C., Ingegnoli, F., Borzi, E., Cantone, L., Coletto, L. A., Stefania Rizzuto, A., De Lucia, O., Briguglio, S., Ruscica, M., Caporali, R., Bollati, V., Buoli, M., and Antonucci, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Cells
• Publisher: MDPI
• ISSN: 2073-4409
• ISSN (Online): 2073-4409
• Copyright Holders: Copyright © 2022 by the authors
• First Published: First published in Cells 11(15):2276
• Publisher Policy: Reproduced under a creative commons licence