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.
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.”
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
- Stem cell therapy provides high success rate in paralyzed animals: Turkish veton March 29, 2023 at 5:55 pm
Therapy also preferred in treatment of various eye, joint, liver, kidney, heart, skin, inflammatory bowel diseases in animals - Anadolu Agency ...
- Top "Nerve Repair and Regeneration Market" Share 2023-2031, With 124 Pageson March 28, 2023 at 6:05 pm
Report Highlights with 124 pages: -"The global Nerve Repair and Regeneration market size was valued at USD 11835.78 ...
- MDA 2023: Designer DNA drug for ALS shows promise in mouse studieson March 28, 2023 at 10:32 am
A new designer DNA therapy that aims to restore stathmin-2 protein levels in ALS has shown promise in early mouse studies.
- Collagen Matrix Inc. Unveils New Brand and Name as Regenity Bioscienceson March 28, 2023 at 8:00 am
The rebrand supports the company's position as material transformers in regenerative implant scienceOAKLAND, N.J., March 28, 2023 /PRNewswire/ -- ...
- Nerve Repair and Regeneration Market Top Players By 2031on March 27, 2023 at 6:12 pm
The "Nerve Repair and Regeneration Market" study describes how the technology industry is evolving and how major ...
- New Brain Implant Device Could Restore Function in Paralyzed Limbson March 26, 2023 at 1:19 pm
A brain implant that can restore arm and leg movements has been developed by British scientists to boost connections between neurons and the paralyzed limbs, offering hope to accident victims. The ...
- New “Biohybrid” Neural Implant Could Restore Function in Paralyzed Limbson March 24, 2023 at 8:37 am
Researchers have developed a new type of neural implant that could restore limb function to amputees and others who have lost the use of their arms or legs. In a study carried out in rats, researchers ...
- Human stem cells used to create new type of biohybrid neural implanton March 22, 2023 at 7:28 pm
Researchers at the University of Cambridge have developed a new type of neural implant that combines stem cells with electronics and has the potential to help amputees or those who’ve lost the use of ...
- Brain implant that restores arm, leg movements developed by scientistson March 22, 2023 at 11:10 am
It worked in rats that had lost the use of their arms - meaning paralyzed patients may be able to get back mobility. The "biohybrid" device combines flexible electronics and human stem cells – the ...
via Bing News