For the brain to function correctly, the cells of the central nervous system must be able to communicate among themselves. A research team at the Johannes Gutenberg University in Mainz described a new method of communication between some of these cells. They revealed the role and functioning of vesicles containing the nutrients necessary for maintaining the neurons in good health. Better understanding of this neuronal activity casts a new light on some degenerative diseases and could have therapeutic applications.
Cet article existe également en français : “Les exosomes, ou comment les neurones se régénèrent”. Il a été traduit du français par Timothée Froelich.
Electron microscopy of axonal vesicles
Source: Laboratory of Eva-Maria Krämer-Albers
The central nervous system allows information to circulate between the brain and the rest of the body. It is composed of several types of cells: neurons and glial cells, which in turn are divided into several categories, like the oligodendrocytes. Each has a specific role to play. Neurons transmit messages. Glial cells hold neurons in place, isolate them from each other, bring them nutrients, modulate their responses and destroy pathogens and dead neurons.
Researchers looked at the relationships between oligodendrocytes and neurons. In an article published in PLOS Biology and available on MSW, they revealed a new channel of communication between these cells.
Neurons and oligodendrocytes: an intimate relationship
Neurons are very elongated cells that form a real network of cellular interconnections. Information is passed from one neuron to its target via its axon, a filament that can extend more than a meter. To make the signal circulate faster, this extension is covered by a myelin sheath produced by the surrounding cells, the oligodendrocytes. The information is transmitted between the cells as an electrical signal that goes faster by jumping between the different sheaths than by running along the length of the axon.
Neurons and oligodendrocytes
Figure adapted from Neurotransmitter –Triggered Transfer of Exosomes Mediates Oligodendrocyte– Neuron Communication. PLoS Biol 11(7): e1001604. doi:10.1371/journal.pbio.1001604
For healthy functioning of the brain, it is necessary for the neurons and their neighbors, the glial cells, to communicate well. The latter are known for the crucial role they play in keeping neurons healthy, but how do they actually do that? A first element of a response has been put forward by Eva-Maria Krämer-Albers et al. from the Johannes Gutenberg University in Mainz.
Exosomes, regenerative vesicles for neurons
When needed, neurons can send a signal to oligodendrocytes, which provide them with vesicles called exosomes. These are liberated by the myelin sheath and then retrieved by neurons. The vesicles contain many different molecules: proteins, lipids, and genetic material. They bring all they nutrients required for the regeneration of active neurons. “They are just like packets of “cleaningproducts” involved in the long-term axon maintenance process,” explains Prof. Krämer-Albers.
Some neurodegenerative diseases are related to a problem affecting the myelin. In the case of multiple sclerosis, the myelin sheaths degrade over time. It is possible, therefore, that exosomes participate in the development of symptoms. Without the myelin, which provides the vesicles, neurons no longer receive enough nutrients and eventually die. The signal can no longer be transmitted between the brain and the muscles. In the advanced form of the disease, patients end up paralyzed.
A possible therapeutic role for exosomes?
The question raised today is whether exosomes can be used as therapeutic agents. For Krämer-Albers, the idea seems promising, but she adds that there is still a long way to go before achieving it.
Diverse studies have already demonstrated that exosomes could be artificially generated. Through intravenous injection or inhalation, it is possible to diffuse the molecules that they contain straight into the brain. The brain is well protected and only a few molecules can reach it. “These particles could be very useful to disseminate therapeutic agents into the brain. These ‘cleaning products’ could become ‘treating products’. But as of now, all of this is still a dream,” says Eva-Maria Krämer-Albers.
Another aspect under study is using exosomes to improve neuronal regeneration. “But before we manage to heal patients, we must keep trying to understand the cellular mechanisms in order to start from solid scientific bases. We will be able to achieve great therapeutic advances tomorrow only by supporting this kind of fundamental research today,” concludes Krämer Albers.
To find out more:
Frühbeis C, Fröhlich D, Kuo WP, Amphornrat J, Thilemann S, et al. (2013) Neurotransmitter-Triggered Transfer of Exosomes Mediates Oligodendrocyte–Neuron Communication, Eva-Maria Krämer-Albers, PLoS Biol 11(7): e1001604. doi:10.1371/journal.pbio.100160,4
Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Molecular Therapy 2011, 19(10):1769-79.
Intranasal Exosomes for Treatment of Neuroinﬂammation?: Prospects and Limitations. Molecular Therapy 2011, 19(10), 1754–1756.
Front page photo:
Neurons trigger the retrograde transport of a myelin protein (green) from late endosomes/lysosomes (red) to the surface of oligodendrocytes. (JCB 172(6) TOC1)
Reference: Trajkovic et al. (2006) J. Cell Biol. 172:937-948.
Published on: March 6, 2006.
This image is available to the public to copy, distribute, or display under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license.
Source: Flickr / TheJCB