Exosomes From Astrocyte Processes: Signaling to Neurons

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.

Extracellular Neuroglobin as a Stress-Induced Factor Activating Pre-Adaptation Mechanisms against Oxidative Stress and Chemotherapy-Induced Cell Death in Breast Cancer

“…A great amount of globin co-localizes with collagen fibers, suggesting that NGB can be released by breast cancer cells in vivo. This result, in line with evidence demonstrating the presence of NGB in astrocytes derived exosomes [ 11 ], in serum of animal models after ischemic-reperfusion insults [ 40 ], and in plasma of human patients with traumatic brain injury [ 41 ], indicates that the extracellular NGB release is a common feature of this globin.…”

“…Indeed, during the last years, the idea that NGB localization may provide some clues about its function and that stimuli able to change NGB level/localization might also affect such function, has earned growing interest [ 8 , 33 , 36 , 37 , 38 ]. Other independent studies further complicate this scenario, indicating that NGB may be released from astrocytes [ 11 ] and exogenous NGB can exert cytoprotective functions in astroglial cells [ 12 ] and retinal neurons [ 39 ].…”

“…At least four types of non-classical protein secretion have been distinguished and they comprise the direct translocation across the membrane (Type I and Type II), the organelle-based translocation (autophagosome, endosome, and exosomes, Type III) and the ER-based translocation with Golgi bypass (Type IV) [ 42 , 43 , 46 ]. Although NGB may follow one or more of the different mechanisms of non-classical protein secretion, the finding of NGB in astrocytes-derived exosomes [ 11 ] suggests that the exosome-mediated mechanism may be directly involved in the globin release also in breast cancer cells. However, the definition of the specific UPS involved in NGB release warrant further studies, and our research group is strongly addressing this aim.…”

“…Indeed, in ERα+ breast cancer cells, high level of E2-induced NGB takes part in the ERα-dependent pathways committed to the anti-apoptotic response against oxidative stress [ 7 ] and paclitaxel, a chemotherapeutic agent [ 9 ]; moreover, NGB participates in the E2-induced anti-oxidant effects through the NRF-2 pathway [ 10 ]. Recently, NGB was found in astrocyte-derived exosomes [ 11 ], and treatment with sub-nanomolar concentration of extracellular NGB induces a protective effect against oxidative stress and apoptotic cell death in astroglial cells [ 12 ]. These data sustain the idea that NGB could be released in the extracellular milieu where the globin could elicit its pro-survival functions outside the cells.…”

Sensitivity of the Fasciae to the Endocannabinoid System: Production of Hyaluronan-Rich Vesicles and Potential Peripheral Effects of Cannabinoids in Fascial Tissue

“…It is widely recognized that extracellular vesicles constitute a fundamental signal transmission in the central nervous system. Venturini and coauthors recently demonstrated that astrocytes are able to convey messages and transfer neuroglobin through extracellular vesicles, which selectively target neurons [18]. However, it is widely recognized that different cell types can release micro-vesicles, which operate as mediator of the inter-cellular communication ensuring short-and long-range exchange of information [19,20].…”