Abstract

Astrocytes have long been considered as just providing trophic support for neurons in the central nervous system. However, from few decades ago, several studies have demonstrated astrocytic importance in many functions such as neurotransmission, redox balance, metabolite and electrolyte homeostasis, among others. Ascorbic acid is a powerful antioxidant which is concentrated in brain. During synaptic activity ascorbic acid is released by astrocytes and taken up by neuronal cells. In neurons ascorbic acid is utilized to maintain redox balance and to modulate neuronal metabolism. Molecular and cellular basis of ascorbic release is not fully understood. In this work we studied ascorbic acid release from astrocytes through exosomes, extracellular microvesicles and hemichannels. Microvesicles and exosomes were purified from supernatant of primary cultures of cortical astroglial cells and human astrocytes cell line by centrifugation and ultracentrifugation, respectively. HPLC-detected ascorbic acid was released through exosomes and microvesicles in astrocytes. Also, the application of LaCl3, a hemichannel inhibitor, decreased ascorbic acid efflux suggesting an important role of connexins in ascorbic acid release from astrocytes. Finally, we demonstrated that ascorbic acid-containing exosomes derived from astrocytes is able to modulates the expression pattern of proteins related to ascorbic acid recycling and homeostasis in neuronal cells. Mechanisms of ascorbic acid exportation form glial to neuronal cells are indispensable to maintain the correct neuronal function. Impaired ascorbic acid release through these mechanisms could be related to redox and metabolic failures described in neurodegenerative diseases.