Medicinal Leech CNS as a Model for Exosome Studies in the Crosstalk between Microglia and Neurons

Antonella Raffo-Romero, Tanina Arab, Issa S Al-Amri, Francoise Le Marrec-Croq, Christelle Van Camp, Quentin Lemaire, Michel Salzet, Jacopo Vizioli, Pierre-Eric Sautiere, Christophe Lefebvre,

Int J Mol Sci

https://doi.org/10.3390/ijms19124124

Abstract

In healthy or pathological brains, the neuroinflammatory state is supported by a strong communication involving microglia and neurons. Recent studies indicate that extracellular vesicles (EVs), including exosomes and microvesicles, play a key role in the physiological interactions between cells allowing central nervous system (CNS) development and/or integrity. The present report used medicinal leech CNS to investigate microglia/neuron crosstalk from ex vivo approaches as well as primary cultures. The results demonstrated a large production of exosomes from microglia. Their incubation to primary neuronal cultures showed a strong interaction with neurites. In addition, neurite outgrowth assays demonstrated microglia exosomes to exhibit significant neurotrophic activities using at least a Transforming Growth Factor beta (TGF-β) family member, called nGDF (nervous Growth/Differentiation Factor). Of interest, the results also showed an EV-mediated dialog between leech microglia and rat cells highlighting this communication to be more a matter of molecules than of species. Taken together, the present report brings a new insight into the microglia/neuron crosstalk in CNS and would help deciphering the molecular evolution of such a cell communication in brain.