Exosomes From Astrocyte Processes: Signaling to Neurons.

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

doi:10.3389/fphar.2019.01452

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.

Highlights

The relevance of neuron-astrocyte network function in the intercellular communication in central nervous system (CNS) as well as in the vulnerability to neurodegenerative and neuropsychiatric diseases is widely accepted
We report for the first time that astrocytic processes freshly prepared from adult rat cerebral cortex and originating from astrocytes that have matured in astrocyte-neuron networks, are provided with structures resembling multivesicular bodies and can release vesicles, which exhibit the features of exosomes
We show that the nerve terminals prepared from rat cerebral cortex were positive for synaptophysin and negative for glial fibrillary protein (GFAP) (Figures 1J–L)

Summary

Introduction

The relevance of neuron-astrocyte network function in the intercellular communication in central nervous system (CNS) as well as in the vulnerability to neurodegenerative and neuropsychiatric diseases is widely accepted (see Halassa and Haydon, 2010; Sofroniew, 2015; Verkhratsky et al, 2016). In the neuron-astrocyte networks the perisynaptic astrocyte processes function as sensors of transmitters in the extracellular environment —acted upon by neurotransmitters and gliotransmitters through a volume transmission mode of communication (see for reviews Agnati and Fuxe, 2000; Vizi, 2000)—and modulate neural activity by clearing glutamate and by releasing gliotransmitters (see Verkhratsky et al, 2016; Cervetto et al, 2018 and references therein); they regulate extracellular space volume and coverage of synapses (Xie et al, 2013). Various CNS cell types, including neurons, microglia and oligodendroglia, can release exosomes; while cultured astrocytes have been reported to secrete exosomes (see Taylor et al, 2007; Guescini et al, 2010; Wang et al, 2011; Wang et al, 2012; Guitart et al, 2016; Willis et al, 2017; Hira et al, 2018; PascuaMaestro et al, 2019; Pei et al, 2019; Xu et al, 2019; see Verkhratsky et al, 2016 and Lafourcade et al, 2016), less is known on the ability of astrocytes to release exosomes in neuronastrocyte networks

Methods

Results

Discussion

Conclusion