If the entrances and exits of freeways shut down, traffic all over the United States would come to a halt.
In a similar situation, injuries to the brain can make it impossible for neurons to determine information input from output and impedes the ability of the nervous system to operate.
In a recent report in The Journal of Neuroscience, researchers at Baylor College of Medicine and the University of Connecticut Health Center show that this is exactly what happens after nervous system injury.
Complexity of neurons
Neurons are structurally complex with specific parts of the cell responsible for information input, and other parts responsible for information output, said Dr. Matthew N. Rasband, associate professor of neuroscience at Baylor College of Medicine and senior author of the paper. When neurons cannot distinguish between the two activities, the nervous system stops working.
“This is a new way to think about nervous system injuries,” said Rasband. “We have found a new mechanism contributing to the inability of the nervous system to be repaired.”
Molecular fence
Previously, Rasband and his colleagues discovered that the protein ankyrinG builds a ‘molecular fence’ in neurons to maintain the distinction between dendrites (the parts of the cell responsible for information input) and axons (the part of the cell responsible for information output).
AnkyrinG is only found at the axon initial segment, the site where axons begin and dendrites end. Using genetic tricks, the researchers removed this molecular fence, and saw that proteins normally only found in dendrites moved into axons. In effect, they discovered that loss of ankyrinG converted axons (output) into dendrites (input).
Injury destroys protein
In the current study, they extend this previous work to show that nervous system injuries like stroke and nerve crush destroy ankyrinG, leading to neurons that cannot properly distinguish between their inputs and outputs. Although this damage is irreversible, Rasband’s group determined the events leading up to destruction of ankyrinG. They found that after injury, an enzyme gets activated and functions like molecular scissors, cutting ankyrinG into smaller, non-functional pieces. That discovery could be a window of opportunity to use inhibitors of the enzyme to stop the degradation, said Rasband.
“We were successful, but only if the enzyme was inhibited before it destroyed ankyrinG.”
Preservation may be key to treatment
Rasband suggested that their results point to the need for multifaceted treatments for brain injuries and stroke that focus not only on neuroprotection, but also to preserve the axon initial segment and maintain the distinction between axons and dendrites.
Another step forward will be to determine if degradation of ankyrinG is a common event in a variety of brain and spinal cord injuries. With a grant from the U.S. Department of Defense, Rasband’s group is currently studying traumatic brain injury to determine if blast injuries like those experienced by soldiers might also lead to damage of the axon initial segment.
Others who took part in the study include first author Dr. Dorothy P. Schafer, a former graduate student of Rasband and now with Harvard Medical School; Dr. Smita Jha, a postdoctoral fellow in Dr. Rasband’s laboratory in the department of neuroscience at BCM; Dr. Fudong Liu, Trupti Akella and Dr. Louise D. McCullough, all of the department of neuroscience at the University of Connecticut Health Center.
The research was supported by grants from the National Institutes of Health, the Department of Defense, the Dr. Miriam and Sheldon Adelson Medical Research Foundation and Mission Connect.
—
On the Net:
Comments