Ricerc@Sapienza

The importance of microglia-astrocytes cross-talk in the maintenance of brain homeostasis, and in granting neuronal functionality represent a new field of research that is worth to be investigated in order to identify new target to be considered when treating brain disorders. Interplay between cells can be achieved by the release of soluble factors, by cell-to-cell adhesion molecules but also through the exchange of molecular "cargo" via extracellular vesicles such as microvesiscles (MVs). In recent years, the role of chemokines in participating in the cross-talk between cells of the brain parenchyma has also emerged, and in particular we found that chemokine CXCL16, physiologically expressed in the brain, represent an endogenous molecule that counteract brain damage upon ischemic insult. Moreover, we demonstrated that CXCL16, exogenously admninistrated, acts on astrocytes inducing the release of "soluble" mediators that concurr to reduce glutamate excitotoxic neuronal damage.Further we found that CXCL16 is able to contrast microglia polarization towards an inflammatory phenotype. Since glutamate excitotoxicity and inflammatory conditions are both events that occur in several brain disorders, we want to investigate the possibility that MVs, released upon CXCL16 treatment of microglia or astrocytes, might represent a tool to contrast these events; in addition we want to investigate if intranasal administration of such MVs might be able to contrast LPS induced neuroinflammation.