Neuroprotective effects of astrocyte-derived extracellular vesicles

Abstract

Astrocytes are glial cells responsible for neuronal support, and also exert protection against excessive excitation of L-glutamate-responsive neurons through excitatory amino acid transport and protection against reactive oxygen species (ROS). A growing number of studies have shown that astrocytes release extracellular vesicles (EVs) that exert neuroprotective effects. Here we aim to evaluate whether astrocytes overstimulated with L-glutamate overload, or challenged through chemogenetic generation of hydrogen peroxide, release EVs that protect neurons against events associated with excitotoxicity. This phenomenon is caused by high levels of L-glutamate in the synaptic cleft, culminating in the activation of ionotropic glutamate receptors subtypes N-methyl-D-aspartate (NMDA) and ±-amino-3-hidroxi-5-metil-4-isoxazol-propiônico/kainate (AMPA/KA), leading to high calcium influx and ROS production. EVs from astrocytes primary cell culture supernatants will be evaluated in excitotoxicity models in vitro. This mechanism may be relevant to understand injury processes that occur in cerebral ischemia and other types of acute brain injury characterized by a peripheral penumbra region that displays delayed cell death passive of neuroprotection. This project may reveal astrocytes protective roles through an alternative long-distance cell communication system.