Abstract

Exosome Transfer from Glia to Neurons: Trigger of Release, Mechanisms of Uptake, Physiological Impact

Eva-Maria Krämer-Albers, Group Leader, University of Mainz

Brain function depends on coordinated interactions between neurons and glial cells. Oligodendroglia myelinate axons and furthermore provide support mediating long-term axonal integrity. Our recent work revealed that myelinating oligodendrocytes release exosomes in response to neurotransmitter signalling and activation of glial ionotropic glutamate receptors. These exosomes are internalized by neurons via endocytosis and the exosome cargo is functionally recovered by the recipient neurons. Neurons appear to benefit from exosome internalization by increased resistance to stress conditions such as oxidative stress, starvation and ischemia indicating a role of glia to neuron exosome transfer in glial support and neuroprotection. Oligodendroglial exosomes have the ability to modulate a broad spectrum of neuronal functions. Treatment of cultured neurons with isolated glial exosomes affects action potential firing and axonal transport, activates signal transduction pathways, and regulates neuronal gene expression. We further studied exosome release from oligodendrocytes derived from PLP- and CNP-deficient mice, which are characterized by secondary axonal degeneration, and found that exosome secretion in these mouse models is impaired. Intriguingly, exosomes derived from knock-out oligodendrocytes lack neuroprotective activity and the ability to promote axonal transport. In summary, we propose that oligodendroglial exosomes function as vehicles for the transfer of biomolecules from oligodendrocytes to neurons and are implicated in neuroprotection and glial maintenance of axonal integrity. Supported by DFG.