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. Treatment of mice with Pregabalin, a drug that acts upon the growth inhibiting mechanism, caused damaged nerve connections to regenerate.
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.”
The Latest on: Nerve regeneration
[google_news title=”” keyword=”nerve regeneration” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Nerve regeneration
- Researchers develop artificial cell environment to promote nerve regenerationon February 20, 2024 at 8:55 am
Injuries in the central nervous system heal poorly because cavities scar. Researchers hope to remedy this problem by filling the cavities in such a way that stem cells feel comfortable in them.
- Chemical cocktail could restore sight by regenerating optic nerveson February 16, 2024 at 6:00 am
The optic nerve has been partly regenerated in mice, raising hopes for treating blindness caused by conditions such as glaucoma ...
- Top 4 Best Herbs for Nerve Pain in 2024on February 4, 2024 at 4:00 pm
Are there any Chinese or Ayurvedic herbs that can aid in nerve regeneration? Yes, there are several Chinese and Ayurvedic herbs that can aid in nerve regeneration. Some of the most effective ones ...
- Nanomedicine Gives the Way for Nerve Cell Regenerationon December 22, 2023 at 10:08 am
researchers describe the use of nanotechnology to enhance the regeneration of nerve cells. In the first method, developed at the University of Miami, researchers show how magnetic nanoparticles ...
- “Oncomodulin”- Path To Nerve Regenerationon December 22, 2023 at 4:27 am
Absence of nerve regeneration in injured nerve fibres in the mature central nervous system has always baffled scientists and researchers worldwide, but researchers at Children’s Hospital Boston ...
- How depriving nerves of oxygen can help them healon December 19, 2023 at 9:32 pm
Short blasts of air with lower levels of oxygen than normal may be a new way to tackle nerve pain. The treatment, which involves breathing normal air and oxygen depleted air alternately for about half ...
- Neurobiology of Peripheral Nerve Regenerationon May 25, 2023 at 7:54 pm
He summarises current basic ideas about the molecular mechanisms involved in both nerve degeneration and regeneration and what approaches can be used to address it experimentally. Heavily illustrated ...
- Nerve Repair and Grafting in the Upper Extremityon March 5, 2022 at 1:52 am
As our understanding of nerve regeneration biology has improved, the conduits for regeneration have been refined considerably. The ideal conduit would allow inflow of supportive local nutrient ...
- Considering the evolution of regeneration in the central nervous systemon October 1, 2009 at 5:00 am
The emerging view is that most extrinsic factors investigated can have both beneficial and deleterious effects on preserving injured neurons and nerve regeneration depending on extent and timing.
via Bing News