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.
Highlights
Brain disorders have a growing impact on human disability and morbidity worldwide
The etiology of most brain diseases is poorly described, it is clear that pro-inflammatory events in the central nervous system (CNS) lead to neurodegenerative mechanisms and cognitive decline
The medicinal leech (Hirudo medicinalis) CNS is an interesting model in this regard because microglia cells can be studied in close relation with either neuronal cell bodies or axons
Summary
The etiology of most brain diseases is poorly described, it is clear that pro-inflammatory events in the central nervous system (CNS) lead to neurodegenerative mechanisms and cognitive decline. The neuroinflammatory state in the CNS is a broad process involving microglia cells as resident immune cells [1]. The interactions between microglia subpopulations and neurons basically represent a key process of CNS integrity and neuroinflammatory regulations [2,3,4,5]. The medicinal leech (Hirudo medicinalis) CNS is an interesting model in this regard because microglia cells can be studied in close relation with either neuronal cell bodies or axons. Neuronal cell bodies are concentrated in ganglia and project the axons into the connective tissues [6,7]
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