ATHENS, Ohio -- Aided by a microscope and a digital camera, a team of researchers led by an Ohio University cell biologist has snapped the first pictures of a sight that has eluded scientists for 15 years -- tiny threads of protein key to the health of the nervous system darting along nerve fibers.
What they've documented with time-lapse photography could one day lead to a better understanding of nerve malfunction in Lou Gehrig's disease and other, similar neurological disorders.
For the past two decades, scientists have struggled to observe how proteins critical to the growth and maintenance of the nervous system travel through the body's network of nerves. In the March issue of the journal Nature Cell Biology, Anthony Brown, Ohio University associate professor of cell biology, and his colleagues report on a new technique that allowed them to watch and photograph the movement of microscopic threads of protein called neurofilaments in nerve fibers.
A logjam of this neurofilament movement, which blocks other biological processes vital to the nerve's survival, has been seen in patients with certain neurological disorders, such as Lou Gehrig's disease.
"If we can learn something about the way neurofilaments move in nerves, we may get some clues about what possible events could cause them to move abnormally or stop moving," says Brown, principal investigator on the study. "If we understand that, it might have some relevance to these diseases."
The researchers' observation of the neurofilament movement (movies available at http://www.nature.com/ncb//suppl/ncb0300/ncb0300_137/ has provided a rare glimpse of slow axonal transport, the process by which many of the proteins in the nerve cell's cytoplasm travel from the nerve cell body along the nerve fibers, also called axons. These proteins are crucial for the development and maintenance of axons, branch-like fibers that communicate information from the nervous system to other areas of the body.
The study suggests that neurofilaments move in fast but infrequent spurts -- at rates of up to two-thousandths of a millimeter per second. This finding argues against a previous theory of slow axonal transport, which hypothesized that neurofilaments and other transported proteins travel in a slow, steady manner. The long pauses between the quick movements the team observed may be one reason why scientists have had a hard time tracking the process, Brown says.
"It's been very puzzling to people in the field why it's been so difficult to see the movement," he says. "Our paper shows the movement of neurofilaments for the first time in cultured nerve cells. The characteristics we see are very surprising, and it may explain why it was difficult to see in the past."
To make the movement visible, Brown's team fused DNA coding for neurofilament protein with the DNA coding for the protein that makes jellyfish glow green. But as most nerve fibers are packed with neurofilaments along their entire length, at first all the researchers could see was one long bright green strip. The scientists solved the problem by studying nerve cells that had fewer neurofilaments, which showed visible gaps in the green fluorescence. They digitally photographed the movement of the neurofilaments by waiting for them to sprint across these gaps.
"The gaps are basically like little windows on the cytoplasm of the axon," Brown says. "They allow us to see movement that we normally wouldn't be able to see. That really was the key."
Now that the researchers have observed neurofilaments in transit, Brown's laboratory will begin the study of how the proteins move. "Only once we understand the mechanism of movement, can we really start to understand the mechanism that might impair movement," Brown says.
The paper was co-authored by Lei Wang, an Ohio University graduate student in Brown's laboratory, and Chung-liang Ho, Dongming Sun and Ronald Liem of the Columbia University College of Physicians and Surgeons. The research was funded by the National Institute of Neurological Disorders and Stroke.
Brown holds an appointment in the College of Arts and Sciences.
Written by Andrea Gibson.
Attention Editors, Reporters: The article in the March issue of Nature Cell Biology is available online at http://www.nature.com/ncb. To view a movie of the nerve activity described here, go to http://www.nature.com/ncb//suppl/ncb0300/ncb0300_137/. A cutline follows this release.
Contact: Andrea Gibson (740) 597-2166, gibsona@ohio.edu; after March 29, Anthony Brown (740) 593-2330, browna1@ohio.edu
Cutline: Neurofilament proteins move quickly but infrequently along axons.
Journal
Nature Cell Biology