Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers activate repair program for nerve fibers

07.10.2016

Releasing molecular brake allowed damaged neurons to regenerate

Injuries to the spinal cord can cause paralysis and other permanent disabilities because severed nerve fibers do not regrow. Now, scientists of the German Center for Neurodegenerative Diseases (DZNE) have succeeded in releasing a molecular brake that prevents the regeneration of nerve connections.


DZNE scientists have identified a molecular brake that prevents the regeneration of nerve connections. To this end large sets of genomic data had to be analyzed. This is illustrated in the above figure. Image: DZNE/A. Tedeschi

Treatment of mice with “Pregabalin”, a drug that acts upon the growth inhibiting mechanism, caused damaged nerve connections to regenerate. Researchers led by neurobiologist Frank Bradke report on these findings in the journal “Neuron”.

Human nerve cells are interconnected in a network that extends to all parts of the body. In this way control signals are transmitted from head to toe, while sensory inputs flow in the opposite direction. For this to happen, impulses are passed from neuron to neuron, not unlike a relay race. Damages to this wiring system can have drastic consequences – particularly if they affect the brain or the spinal cord. This is because the cells of the central nervous system are connected by long projections. When severed, these projections, which are called “axons”, are unable to regrow.

Reawakening a lost talent

Neural pathways that have been injured can only regenerate if new connections arise between the affected cells. In a sense, the neurons have to stretch out their arms, i.e. the axons have to grow. In fact, this happens in the early stages of embryonic development. However, this ability disappears in the adult. Can it be reactivated? This was the question Professor Bradke and co-workers asked themselves. “We started from the hypothesis that neurons actively down-regulate their growth program once they have reached other cells, so that they don’t overshoot the mark. This means, there should be a braking mechanism that is triggered as soon as a neuron connects to others,” says Dr. Andrea Tedeschi, a member of the Bradke Lab and first author of the current publication.

Searching through the genome

In mice and cell cultures, the scientists started an extensive search for genes that regulate the growth of neurons. “That was like looking for the proverbial needle in the haystack. There are hundreds of active genes in every nerve cell, depending on its stage of development. To analyze the large data set we heavily relied on bioinformatics. To this end, we cooperated closely with colleagues at the University of Bonn,” says Bradke. “Ultimately, we were able to identify a promising candidate. This gene, known as Cacna2d2, plays an important role in synapse formation and function, in other words in bridging the final gap between nerve cells.” During further experiments, the researchers modified the gene’s activity, e.g. by deactivating it. In this way, they were able to prove that Cacna2d2 does actually influence axonal growth and the regeneration of nerve fibers.

Pregabalin triggered neuronal growth

Cacna2d2 encodes the blueprint of a protein that is part of a larger molecular complex. The protein anchors ion channels in the cell membrane that regulate the flow of calcium particles into the cell. Calcium levels affect cellular processes such as the release of neurotransmitters. These ion channels are therefore essential for the communication between neurons.

In further investigations, the researchers used Pregabalin (PGB), a drug that had long been known to bind to the molecular anchors of calcium channels. Over a period of several weeks, they administered PGB to mice with spinal cord injuries. As it turned out, this treatment caused new nerve connections to grow.

“Our study shows that synapse formation acts as a powerful switch that restrains axonal growth. A clinically-relevant drug can manipulate this effect,” says Bradke. In fact, PGB is already being used to treat lesions of the spinal cord, albeit it is applied as a pain killer and relatively late after the injury has occurred. “PGB might have a regenerative effect in patients, if it is given soon enough. In the long term this could lead to a new treatment approach. However, we don’t know yet.”

A new mechanism?

In previous studies, the DZNE researchers showed that certain cancer drugs can also cause damaged nerve connections to regrow. The main protagonists in this process are the “microtubules”, long protein complexes that stabilize the cell body. When the microtubules grow, axons do as well. Is there a connection between the different findings? “We don’t know whether these mechanisms are independent or whether they are somehow related,” says Bradke. “This is something we want to examine more closely in the future.”

Original Publication
„The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS“, Andrea Tedeschi, Sebastian Dupraz, Claudia J. Laskowski, Jia Xue, Thomas Ulas, Marc Beyer, Joachim L. Schultze, Frank Bradke, Neuron, DOI: http://dx.doi.org/10.1016/j.neuron.2016.09.026

Weitere Informationen:

https://www.dzne.de/en/about-us/public-relations/news/2016/press-release-no-16.h...

Dr. Marcus Neitzert | idw - Informationsdienst Wissenschaft

Further reports about: DZNE nerve cells nerve fibers neurons spinal spinal cord synapse formation

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>