Biophysicists reveal new picture of nervous system function
Study may improve understanding of health disorders such as Lou Gehrig’s disease
By Adam Liebendorfer
April 18, 2012
Although scientists know that neurofilaments play an important role in the human nervous system, for 20 years they’ve been debating how these pieces move. Ohio University physicist Peter Jung, his doctoral student Yinyun Li and fellow researchers are closer to pinning down the answer, which could provide a better understanding about what causes nerve disorders such as Lou Gehrig’s disease.
Nerve cells are linked by axons, which carry a charge from the cell’s nucleus to other cells. Inside these axons are thousands of tightly packed neurofilaments, which give the axon its shape. These neurofilaments move very slowly, and biophysicists have struggled to explain their activity. Many once believed there were two types of neurofilaments: stationery ones that prop up the cell’s skeleton and mobile ones that float along and give axons their size.
In a recently published and highlighted paper in the Journal of Neuroscience, however, Li and Jung found that the axon is like a subway line on which neurofilaments move like rickety cars. Neurofilaments spend most of their time sitting off the track, and when they finally move up and down the line, they do so only in short bursts.
That part of the model is still being worked through, but Jung offers another analogy to summarize the findings to date.
“Imagine a drunkard walking along the street with many bars,” he says. “He goes in a bar and he stops there for a little bit. Then he goes along a little farther and finds another one. It’s very slow.”
Li says she felt “both surprised and excited” when they found that their model worked to predict how the neurofilaments moved.
Exactly what controls how neurofilaments move is still left to conjecture, but Jung believes it has something to do with the myelin, a sheath that forms around sections of the axon and gives the axon its sausage-like look. The body produces myelin to allow nerve cells to send electric signals faster.
The slower neurofilaments move, the bigger the axons are in size, which allows them to carry an even stronger electric charge to other neurons. But only up to a point. The body normally keeps neurofilaments from bunching up in a single section of the axon.
In certain diseases, such as Lou Gehrig’s disease, Jung hypothesizes that a section of the axon dams up and becomes swollen with backed up neurofilaments. If a section gets too bloated, it will fail to conduct the electric current it’s supposed to carry and the neural signal dies.
Jung, supported by the National Science Foundation, started investigating neurofilaments a decade ago. Working jointly with researchers at Ohio State University, he published a model for how neurofilaments normally move in 2009. Team members in Columbus tried several ways to track neurofilaments in an axon—no easy feat for something that’s 5 microns long, changes shape and can move erratically in either direction. They eventually settled on coding a section of neurofilaments with a laser and measuring how it dispersed. From that data, Jung and student researchers derived a model to predict how the neurofilaments move.
“The main problem is you can’t get a few neurons of people that have (Lou Gehrig’s disease) very easily when they’re starting to block up,” he says.
Now Jung and his fellow researchers hope to model Lou Gehrig’s disease. They’re still planning and drafting research proposals, but he says the experiment would revolve around taking a nerve cell ex vivo, or out of an organism, and subjecting it to a drug that would simulate the disease.
As for Li, she’ll be on the research team as a doctoral student for one more year. After that, she plans to pursue a postdoctoral research fellow position in computational biophysics.
“I feel I am really lucky that I can work with Dr. Jung in the biophysics program,” she says. “It’s a very good starting point of a research career.”
Related content: "Making the Connections," a profile of Distinguished Professor Peter Jung, Spring/Summer 2010 issue of Ohio University's Perspectives magazine.