In Vitro Effects of Cocaine on Tunneling Nanotube Formation and Extracellular Vesicle Release in Glioblastoma Cell Cultures

Abstract

The effects of cocaine (150 nM, 300 nM, and 150 μM) on human glioblastoma cell cultures were studied on tunneling nanotube formation (1-h cocaine treatment) and extracellular vesicle release (1-, 3-, and 8-h cocaine treatment). Cocaine significantly increased the number of tunneling nanotubes only at the lowest concentration used. The release of extracellular vesicles (mainly exosomes) into the medium was stimulated by cocaine at each concentration used with a maximum effect at the highest concentration tested (150 μM). Moreover, cocaine (150 nM) significantly increased the number of vesicles with 61-80 nm diameter while at concentrations of 300 nM and 150 μM, and the smaller vesicles (30-40 nm diameter) were significantly increased with a reduction of the larger vesicles (41-60 nm diameter). A time dependence in the release of extracellular vesicles was observed. In view of the proposed role of these novel intercellular communication modes in the glial-neuronal plasticity, it seems possible that they can participate in the processes leading to cocaine addiction. The molecular target/s involved in these cocaine effects could be specific molecular components of plasma membrane lipid rafts and/or cocaine-induced modifications in cytoplasmic lipid composition.

Effect of prolonged freezing of semen on exosome recovery and biologic activity

“…Therefore, it is probable that illicit drug use alters the composition of exosomes during biogenesis due to its cellular affects. The impact of drug use on the exosomal pathway is further exemplified by the observation that cocaine enhanced the release of extracellular vesicles in cell cultures20. Indeed, the effect of illicit drugs goes beyond enhancement of HIV-1 infection.…”

Rhes Tunnels: A Radical New Way of Communication in the Brain's Striatum?

“…[ 66 ] Human glioblastoma cells also connect via TNTs. [ 67 ] Prion proteins are found to be transported by TNTs in CAD (Cath.‐a‐differentiated) cells, a central nervous system‐derived catecholaminergic neuronal cell line. [ 68,69 ] Studies revealed the presence of TNTs in microvascular endothelial cells and transporting lysosomes and mitochondria.…”

Extracellular vesicles and intercellular communication within the nervous system

“…The tumor transition is typified by a shift from a less aggressive, proneural subtype of GBM to a more aggressive mesenchymal subtype (102), which may be mediated in part by GSC EVs (89). Changes in the tumor microenvironment are undoubtedly achieved through combinatorial "armaments," as recipient cells are bombarded not only with EVs containing many proteins, lipids, and RNA species, but also with the secretome of the tumor and potentially with tunneling nanotubes opening direct communication between cells (103). Communication between GBM EVs and the body.…”