New research may lead to techniques for jump-starting the faulty "wiring" in damaged nerve cells and suggests possible avenues for treating spinal cord injuries, Parkinson's disease and amyotrophic lateral sclerosis, or ALS, also known as Lou Gehrig's disease.
University of Houston scientists studying how spinal nerve cells in chicken embryos develop and function have found that chemicals called growth factors play a key role in regulating how embryonic nerve cells acquire the ability to start processing information.
"In some cases, when nerves are damaged or succumb to neurodegenerative diseases such as ALS and Parkinson's, they don't die, but they quit working and may actually revert to an immature embryonic-like state," says Stuart Dryer, a neuroscientist in the department of biology and biochemistry at UH.
Embryonic nerve cells are able to fire electrical impulses shortly after the cells have divided for the last time -- after they are "born." But these impulses are extremely generic, and not necessarily specialized for the kind of information the cell is going to eventually process, Dryer says.
"Initially, the cells are becoming connected, like the individual circuit elements in a computer, and the message that gets through is one that says 'I'm hooking up' rather than 'I'm processing information'," Dryer says. The developing embryonic cells must somehow acquire the ability to discharge and route electrical impulses in a coordinated, highly specialized fashion.
"If damaged cells have indeed entered a kind of immature state, perhaps we can kick-start them back to their proper function using the natural pathways embryonic cells take to become fully functioning nerve cells," Dryer says.
Nerve cells, or neurons, connect to each other in complex networks, carrying electrical and chemical signals through the body to other cells, or "target" tissues, allowing muscles to move and the brain to think.
Dryer's research shows that chemicals -- called growth factors -- may be the trigger that allows embryonic nerve cells to become specialized.
Growth factors secreted by the target tissue signal the embryonic nerve cells to make their own set of chemicals, called ion channel proteins. These ion channel proteins then attach to certain places on the nerve cell's membrane, where they "channel" electrically charged particles called ions in and out of the neuron. This results in the cells becoming able to conduct electrical impulses.
In their most recent study, Dryer and postdoctoral fellow Miguel Martin-Caraballo found that as the number of ion channels increases, the electrical properties of the developing neuron change.
Dryer found that once a certain density of ion channels in the embryonic nerve cell are in place, the cell exhibits mature electrical behavior, functioning with the specialized electrical patterns needed "to do what it's supposed to do," he says. "It is the growth factors associated with the target tissue that spur the ion channel formation. This study is the first attempt to look at how growth factors control the electrical properties of embryonic spinal motoneurons."
Dryer's study is published in the Jan. 1 issue of the Journal of Neuroscience. It was funded by the Muscular Dystrophy Association and the National Institutes of Health. More information on Dryer's research can be found at this URL.
Since 1988, Dryer has been investigating what happens during the development of embryonic neurons that allows these cells to become functionally mature. Understanding these mechanisms may lead to treatments for jump-starting, or rewiring, damaged nerve cells and restoring their function, he says.
"The growth factor molecules secreted by muscle tissue and other nerve cells seem to be the signal that says 'change your electrical properties to become mature'," Dryer says. His research also suggests that the formation of spaces, or synapses, between neurons, and between neurons and their target tissue, is crucial for neurons to become functionally mature, and that growth factors are involved in synapse formation as well.
"The very refined electrical impulses occur after the cells form their synaptic connections, after they hook up with other cells," he says. Growth molecules have been used in clinical trials to treat ALS, with mixed results, Dryer says. "In some of these cases, they may have halted the progression of the disease, but the patients' symptoms didn't get better. Although the nerve cells lived, they may have reverted to an immature state. Perhaps the cells need some other growth factor to jump-start them back into electrical action."
Similarly, some Parkinson's patients have been treated by having embryonic stem cells injected into their brains. "When this approach works, the results can be dramatic, but usually it doesn't work. Why?" Dryer asks. "One possibility is that because they are embryonic cells, they may wire up OK, but perhaps they need another switch that tells them to become not just functional, but specialized with certain electrical behavior. Just because they're in the brain's environment there's no reason to believe they will automatically acquire the ability to become specialized."
(Editor's Note: Video excerpts from an interview with Stuart Dryer are available at this URL.)
[Contact: Stuart Dryer, Amanda Siegfried]