Exosomes From Astrocyte Processes: Signaling to Neurons

Arianna Venturini; Mario Passalacqua; Simone Pelassa; Fabio Pastorino; Mariateresa Tedesco; Katia Cortese; Maria Cristina Gagliani; Giuseppina Leo; Guido Maura; Diego Guidolin; Luigi F Agnati; Manuela Marcoli; Chiara Cervetto

doi:10.3389/fphar.2019.01452

Exosomes From Astrocyte Processes: Signaling to Neurons

Front Pharmacol. 2019 Dec 2:10:1452. doi: 10.3389/fphar.2019.01452. eCollection 2019.

Authors

Affiliations

¹ Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genova, Genova, Italy.
² Section of Biochemistry, Department of Experimental Medicine, and Italian Institute of Biostructures and Biosystems, University of Genova, Genova, Italy.
³ Laboratory of Experimental Therapies in Oncology, IRCCS Istituto G. Gaslini, Genova, Italy.
⁴ 3BrainAG, Wädenswil, Switzerland.
⁵ Department of Informatics, Bioengineering, Robotics and System Engineering DIBRIS, University of Genova, Genova, Italy.
⁶ Section of Anatomy, Department of Experimental Medicine, University of Genova, Genova, Italy.
⁷ Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
⁸ Department of Neurosciences, University of Padova, Padova, Italy.
⁹ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
¹⁰ Centre of Excellence for Biomedical Research CEBR, University of Genova, Genova, Italy.

Abstract

It is widely recognized that extracellular vesicles subserve non-classical signal transmission in the central nervous system. Here we assess if the astrocyte processes, that are recognized to play crucial roles in intercellular communication at the synapses and in neuron-astrocyte networks, could convey messages through extracellular vesicles. Our findings indicate, for the first time that freshly isolated astrocyte processes prepared from adult rat cerebral cortex, can indeed participate to signal transmission in central nervous system by releasing exosomes that by volume transmission might target near or long-distance sites. It is noteworthy that the exosomes released from the astrocyte processes proved ability to selectively target neurons. The astrocyte-derived exosomes were proven positive for neuroglobin, a protein functioning as neuroprotectant against cell insult; the possibility that exosomes might transfer neuroglobin to neurons would add a mechanism to the potential astrocytic neuroprotectant activity. Notably, the exosomes released from the processes of astrocytes maintained markers, which prove their parental astrocytic origin. This potentially allows the assessment of the cellular origin of exosomes that might be recovered from body fluids.

Keywords: adult astrocytes; astrocyte processes; cerebral cortex; ex-vivo; exosomes; extracellular vesicles; neuroglobin; neuron-astrocyte cocultures.