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
- Nerve Repair and Regeneration Market Beyond the Horizon Envisioning the Future of Market Size Analysison April 25, 2024 at 9:46 pm
Nerve Repair and Regeneration Market is valued approximately at USD 5.72 billion in 2019 and is anticipated to grow with a healthy growth rate of more than 9.15% over the forecast period 2020-2027.
- Salt Water Trick For Sleep And Metabolic Regeneration: Does Renew Salt Water Trick Improve Sleep Quality?on April 25, 2024 at 7:33 pm
This is why more research and focus are provided to the sleep support, metabolic regeneration, and weight loss benefits ... drinking this solution every day in moderation will help boost nerve and ...
- Completely New Use Discovered – This Traditional Herb Has Remarkable Nerve Regenerative Propertieson April 25, 2024 at 4:01 pm
Blessed thistle (Cnicus benedictus), a member of the Asteraceae family, thrives in our climate. This plant has been utilized for centuries as a medicinal herb, often consumed as an extract or tea to ...
- Thistle extract accelerates nerve regeneration by up to 29%on April 22, 2024 at 8:49 pm
Nature has again proven effective in treating health conditions, this time nerve injury. According to a new study, a compound found in the blessed thistle plant accelerates the regeneration of damaged ...
- Blessed Thistle's Healing Power: Cnicin's Pharmacokinetics and Axon Regrowth Discoveredon April 22, 2024 at 3:51 pm
Read more about this promising plant extract to aid drug development for nerve injury. | Drug Discovery And Development ...
- New compound from blessed thistle promotes functional nerve regenerationon April 22, 2024 at 11:34 am
Blessed thistle (Cnicus benedictus) is a plant in the family Asteraceae. For centuries, it has been used as a medicinal herb as an extract or tea, e.g. to aid the digestive system. Researchers have ...
- Blessed thistle compound Cnicin speeds nerve growth, study findson April 22, 2024 at 8:34 am
Blessed thistle (Cnicus benedictus) is a plant in the family Asteraceae and also grows in our climate. For centuries, it has been used as a medicinal herb as an extract or tea, e.g. to aid the ...
- New compound from blessed thistle may promote functional nerve regenerationon April 19, 2024 at 11:01 am
Their article "Cnicin promotes functional nerve regeneration" features clinical studies and is published in Phytomedicine. Blessed thistle (Cnicus benedictus) is a plant in the family Asteraceae and ...
- These Are the Types of Mushrooms a Dietitian and Chef Want You To *Dig* Into This Seasonon April 19, 2024 at 9:42 am
To dig (pun intended) a little deeper into the wonderful world of mushrooms, we caught up with Olivia Roszkowski, chef-instructor of Plant-Based Culinary Arts at the Institute of Culinary Education' s ...
via Bing News