http://unisci.com/stories/20021/0121023.htm
21-Jan-2002
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."
Video excerpts from an interview
with Stuart Dryer are available at:
Copyright © 1995-2002 UniSci
Contact: Stuart Dryer, Amanda Siegfried
http://www.uh.edu/admin/media/nr/012002/dryernerve.htm