Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Monday, November 7, 2011

Researchers discover that stem cell marker regulates synapse formation

http://www.physorg.com/news/2011-01-stem-cell-marker-synapse-formation.html

In a study published in the Jan. 30, 2011, advance online edition of , Salk Institute of Biological Studies investigators led by Kuo-Fen Lee, PhD., show that nestin has reason for being in a completely different cell type--muscle tissue. There, it regulates formation of the so-called neuromuscular junction, the contact point between and "their" motor neurons.

Knowing this not only deepens our understanding of signaling mechanisms connecting brain to muscle, but could aid future attempts to strengthen those connections in cases of or spinal cord injury.

"Nestin was a very well known molecule but no one knew what it did in vivo," says Lee, a professor in the Clayton Foundation Laboratories for Peptide Biology. "Ours is the first study to show that it actually has a physiological function."

Previously, researchers knew that as the neuromuscular junction formed in a developing embryo, so-called positive factors cemented connections between incoming and dense clusters of neurotransmitter receptors facing them on . However, in a 2005 Neuron paper Lee defined a counterbalancing factor--the protein cdk5--that whisked away, or dispersed, superfluous muscle receptors lying outside the contact zone, or synapse, so only the most efficient connections were maintained.

The current study addresses how cdk5, which catalytically adds chemical phosphate groups to target proteins, eliminates useless "extrasynaptic" connections. Reasoning that cdk5 must act by chemically modifying a second protein, Jiefei Yang, PhD., a post-doctoral fellow in the Lee lab and the current study's first author, took on the task of finding its accomplice.


He began by eliminating prime suspects in the plethora of proteins found on the muscle side of the synapse. "At the beginning it was like shooting in the dark because cdk5 has so many potential targets at the neuromuscular junction," says Yang. After eliminating the obvious candidates, the team finally considered nestin, based on evidence that cdk5 can phosphorylate nestin in some tissues.

To analyze nestin, the group employed mice in which the positive, synapse-stabilizing factor--known as agrin--had been genetically eliminated. As predicted, microscopic examination of diaphragm muscle tissue in agrin mutant mice showed a complete loss of dense receptor clusters that would mark a mature synapse, meaning that without the agrin "cement," synapse-dispersing activity had swept away the clusters.

However, when agrin mutant mice were administered an RNA reagent that literally knocks out nestin expression, the group made a dramatic finding: the pattern of receptor clusters on diaphragm muscle reappeared, reminiscent of synapses of a normal mouse--meaning that getting rid of nestin allows synapses to proceed even in the absence of the stabilizing glue.

"This in vivo experiment represents a critical genetic finding," explains Lee. "Later, we determined that nestin's basic function is to recruit cdk5 and its co-activators to the muscle membrane, leading to cdk5 activation and initiating the dispersion process." Additional experiments confirmed that nestin is expressed on the muscle side of the neuromuscular junction, in other words, in the "right" place, and that nestin phosphorylation is required for its newfound function.

Lee believes that information revealed by the study could enhance development of tissue replacement therapies. "Currently, in efforts to devise therapies for motor neuron disease or spinal cord injury there is a lot of focus is on how to make neurons survive," he says. "That is important, but we also need to know how to properly form a synapse. If we cannot, the neuromuscular junction won't function correctly."

Yang, who studied animal models of motor neuron disease while a graduate student at USC, agrees. "One long-term goal of this study is to identify ways to inhibit cdk5/nestin," he says. "That could slow synapse deterioration in neuromuscular junction diseases, such as ALS (Lou Gehrig's Disease) or spinal motor atrophy, in which you have an imbalance of positive and negative signals. One approach is to boost positive signaling, but another is to inhibit negative signaling in an effort to slow disease progression."

No comments:

Post a Comment