Tuesday, 23 February 2016

Gene Network Promotes Nerve Regeneration After Injury

Today's post from sciencedaily.com (see link below) is a new finding that's a long way from being what you could call a practical application to be used on humans now but aren't they all? Nevertheless, it's important that we can see where research is going and these studies do increase our knowledge of how our nervous system works. In this case, the end result, if it proves suitable for humans, will only apply to those who have neuropathy caused by direct injury and not those for whom neuropathy is as a result of other factors (most of us). Basically, researchers have found a gene network that actively promotes re-growth of nerve cells and fibres but only after they have been damaged by an external injury. They can also modify an existing drug to further promote regeneration. It doesn't apply to nerve damage in the brain and spinal cord but only to injury of the limbs and thus the peripheral nervous system. Good news you would think but we're still at the mouse-testing stage here, so we're a long way from a treatment for humans. Nevertheless, optimistic projections predict further research into genetic treatments that will eventually lead to wider application. Worth a read, if only to build up your knowledge of your nervous system and how it operates.

Specific gene network found that promotes nervous system repair
Date:February 19, 2016Source:University of California - Los Angeles
Findings an early step toward potential treatments for injuries to the central nervous system

Injured nerve cells in the limbs (the peripheral nervous system or PNS) can regrow and repair. Nerve cells in the central nervous system (CNS) -- brain and spinal cord -- cannot. Now a network of genes has been identified in a mouse study that promotes PNS repair. In addition, an existing drug that mimics that gene network has been repurposed to promote nerve regeneration in the CNS.

Whether or not nerve cells are able to regrow after injury depends on their location in the body. Injured nerve cells in the peripheral nervous system, such as those in the arms and legs, can recover and regrow, at least to some extent. But nerve cells in the central nervous system -- the brain and spinal cord -- can't recover at all.

A UCLA-led collaboration has identified a specific network of genes and a pattern of gene expression mice that promote repair in the peripheral nervous system in a mouse model. This network, the researchers found, does not exist in the central nervous system. The researchers also found a drug that can promote nerve regeneration in the central nervous system.

The study appears in the online edition of the journal Neuron.

Nerve cells throughout the body are responsible for transmitting and receiving electrical messages to cells and tissues in other organ systems. "We know this transmission of messages can be impaired by injury, and the recovery of nerve cells after injury largely depends on their location," said Vijayendran Chandran, a project scientist in the department of neurology at UCLA and the study's first author.

"Understanding these molecular differences in injured nerve cells in the limbs, where regeneration happens, versus injured nerve cells in the spinal cord, where regeneration fails, would open up the possibility to design treatment to enhance neuron regeneration in the central nervous system after injury."

The researchers measured the response of gene regulation at the level of messenger RNA, or mRNA, in each instance of injury. Gene regulation is the process of turning genes on and off, ensuring that genes are expressed at the right times. Messenger RNA carries information from a gene that, in a long molecular cascade, ultimately tells a protein what to do.

The researchers developed a unique set of algorithms to look at the interactions of various groups of genes and the order in which they were expressed.

"That allowed us to find common patterns that correlated with regeneration in the peripheral nervous system, and within those patterns we were able to identify several genes not previously known that enhanced repair," said Dr. Dan Geschwind, the study's senior author and a professor of neurology, psychiatry and human genetics at UCLA.

"But we did not find these patterns in the central nervous system. That was the major advance -- identifying, in an unbiased way, the entire network of pathways turned on in the peripheral nervous system when it regenerates, key aspects of which are missing in the central nervous system."

Next, as a proof of principle that global patterns of gene expression could be used to screen for drugs that mimic the same pattern, the researchers used a publicly available database at the Broad Institute to look for such a drug. That led them to one called Ambroxol, which significantly enhanced central nervous system repair.

"We're excited about this study because there are a number of firsts that came out of it," Geschwind said. "While we still have a long way to go from a mouse study to humans, we present a novel paradigm that has never been applied to the nervous system."

Story Source:

The above post is reprinted from materials provided by University of California - Los Angeles. The original item was written by Mark Wheeler. Note: Materials may be edited for content and length.

Journal Reference:
Daniel H. Geschwind et al. A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. Neuron, February 2016 DOI: 10.1016/j.neuron.2016.01.034


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