Neural stem cell-derived extracellular vesicles favour neuronal differentiation and plasticity under stress conditions.

Extracellular vesicles (EVs) are released by all cell types and are involved in intercellular communication. We evaluated if neural stem cells-derived EVs (NSC-EVs) regulate NSCs proliferation and differentiation under control and stress conditions. We found that NSC-EVs treatment increases cell proliferation and promotes neuronal differentiation and plasticity. The fact that nervous tissue poorly recovers after cellular damage, prump us to evaluate the effect of EVs supplementation under oxidative stress and inflammation. We demonstrate that NSC-EVs restore the proliferative potential of the NSCs affected by oxidative stress. In addition, we provide evidence that oxidative stress and inflammation induce neuronal differentiation. Interestingly, the aberrant cell phenotype induced by inflammation is restored by NSC-EVs treatment, suggesting that these vesicles ameliorate the damage burden in neurons and modulate neuronal plasticity. These results contribute to understand the role of the NSCs-derived EVs as key players for brain tissue generation and regeneration and open new pathways to the development of therapies.

Phosphatidylcholine restores neuronal plasticity of neural stem cells under inflammatory stress.

The balances between NSCs growth and differentiation, and between glial and neuronal differentiation play a key role in brain regeneration after any pathological conditions. It is well known that the nervous tissue shows a poor recovery after injury due to the factors present in the wounded microenvironment, particularly inflammatory factors, that prevent neuronal differentiation. Thus, it is essential to generate a favourable condition for NSCs and conduct them to differentiate towards functional neurons. Here, we show that neuroinflammation has no effect on NSCs proliferation but induces an aberrant neuronal differentiation that gives rise to dystrophic, non-functional neurons. This is perhaps the initial step of brain failure associated to many neurological disorders. Interestingly, we demonstrate that phosphatidylcholine (PtdCho)-enriched media enhances neuronal differentiation even under inflammatory stress by modifying the commitment of post-mitotic cells. The pro-neurogenic effect of PtdCho increases the population of healthy normal neurons. In addition, we provide evidences that this phospholipid ameliorates the damage of neurons and, in consequence, modulates neuronal plasticity. These results contribute to our understanding of NSCs behaviour under inflammatory conditions, opening up new venues to improve neurogenic capacity in the brain.