Home | Pregnancy Timeline | News Alerts | News Archive July 17, 2013

Above: Brain function is determined by the communication between electrically excitable neurons and the surrounding glial cells, which perform many tasks in the brain. Oligodendrocytes are a type of glial cell and these form an insulating myelin sheath around the axons of neurons. If neurons are subjected to stress, cells that have been aided with 'care packages' subsequently recover. Among the substances that are present in the exosomes and are channeled to the neurons are protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes which counter oxidative stress. Image Credit:Learn Genetics, The University of Utah http://learn.genetics.utah.edu/content/begin/cells/badcom/

Glial cells send protective proteins and genetic information to nerve cells

A new mode of cell communication to the nerves is discovered in the brain.

Researchers at Johannes Gutenberg University Mainz (JGU) have discovered a new form of communication between different cell types in the brain. Nerve cells interact with neighboring glial cells, which results in a transfer of protein and genetic information. Nerve cells are thus protected against stressful growth conditions.

The study undertaken by the Mainz-based cell biologists shows how reciprocal communication between the different cell types contributes to neuronal integrity. Their results have been recently published in the journal PLOS Biology.*

Brain function is determined by the communication between electrically excitable neurons and the surrounding glial cells, which perform many tasks in the brain. Oligodendrocytes are a type of glial cell and these form an insulating myelin sheath around the axons of neurons.

In addition to providing this protective insulation, oligodendrocytes also help sustain neurons in other ways that are not yet fully understood. If this support becomes unavailable, axons can die off. This is what happens in many forms of myelin disorders, such as multiple sclerosis, and it results in a permanent loss of neuron impulse transmission.

Like other types of cell, oligodendrocytes also secrete small vesicles. In addition to lipids and proteins, these membrane-enclosed transport packages also contain ribonucleic acids, in other words, genetic information.

In their study, Carsten Frühbeis, Dominik Fröhlich, and Wen Ping Kuo of the Institute of Molecular Cell Biology at Johannes Gutenberg University Mainz found that oligodendrocytes release nano-vesicles known as 'exosomes' in response to neuronal signals.

These exosomes are taken up by the neurons and their cargo can then be used for neuronal metabolism. "This works on a kind of ‘delivery on call’ principle," explained Dr. Eva-Maria Krämer-Albers, who is leading the current study. "We believe that what are being delivered are 'care packages' that are sent by the oligodendrocytes to neurons."

While studying cell cultures, the research group discovered that the release of exosomes is triggered by the neurotransmitter glutamate.

By means of labeling them with reporter enzymes, the researchers were able to elegantly demonstrate that the small vesicles are absorbed into the interior of the neurons.

"The entire package of substances, including the genetic information, is apparently utilized by the neurons," said Krämer-Albers. If neurons are subjected to stress, cells that have been aided with 'care packages' subsequently recover. "This maintenance contributes to the protection of the neurons and probably also leads to synthesis of proteins," states Carsten Frühbeis and Dominik Fröhlich.

Among the substances that are present in the exosomes and are channeled to the neurons are, for instance, protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes which counter oxidative stress.

The study has demonstrated that exosomes from oligodendrocytes participate in a previously unknown form of bidirectional cell communication that could play a significant role in the long-term preservation of nerve fibers.

"An interaction like this, in which an entire package of substances including genetic information is exchanged between cells of the nervous system, has not previously been observed," states Krämer-Albers summarizing the results. "Exosomes are thus similar to viruses in certain respects, with the major difference that they do not inflict damage on the target cells but are instead beneficial."

In the future, the researchers hope to develop exosomes as possible 'cure' packages that could be used in the treatment of nerve disorders.

*Abstract
Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity.

Original press release:http://www.uni-mainz.de/presse/16545_ENG_HTML.php