MU sea lamprey research sheds light on nerve regeneration following spinal cord injury
Nov. 21, 2013
Fish, unlike humans, can regenerate nerve connections and recover normal mobility following an injury to their spinal cord. In an article published in the August issue of Neuroscience, University of Missouri neurobiologist Andrew McClellan sheds light on how the sea lamprey, an eel-like fish, re-grows some of the long nerve “highways” that link the brain to the spinal cord. The findings may guide future efforts to promote recovery in humans who have suffered spinal cord injuries.
The study focuses on the regrowth of a particular group of neurons, called reticulospinal neurons, necessary for locomotion. These neurons, which are found in all vertebrates, are located in the hindbrain and project nerve fibers, or processes, down the spinal cord. When these neurons are damaged, the animal is unable to move below the level of injury. While humans and other higher vertebrates would be permanently paralyzed, the sea lamprey and other lower vertebrates have the ability to regrow these neurons and recover the ability to move within a few short weeks.
“There is a lot of attention to why these neurons regenerate in lower vertebrates and why they don’t in higher vertebrates,” said McClellan, professor of biological sciences in the College of Arts and Sciences and director of the UM Spinal Cord Injury Resarch Program.
In this study, the researchers looked at the role played by small intracellular signaling molecules, called second messengers, in the ability of these neurons to regenerate. Previous studies have shown that these molecules can promote growth of neurons in cell culture and also can improve regeneration in higher vertebrates after an injury. Their effects on reticulospinal neurons, however, had not been studied.
McClellan and his colleagues isolated and removed injured reticulospinal neurons from sea lamprey and grew them in culture. They applied chemicals that activated second messengers and then looked to see what effects they had on these neurons’ growth.
They discovered that activation of a particular second messenger, called cyclic AMP, acted somewhat like an “on” switch, essentially converting neurons from a non-growing state to a growing one. However, it had no effect on neurons that had already begun to grow.
“That sort of makes sense,” said McClellan. “It could very well be that for neurons whose processes are already growing their cyclic AMP levels are moderately high already. Whereas in neurons that are not growing, the levels are low.”
The scientists also report results from neurophysiological experiments that show that cyclic AMP had relatively little effect on the electrical properties of these neurons.
“Our conclusion was that these cyclic AMP pathways do stimulate outgrowth of neural processes in the lamprey, like they do in other neurons, and they don’t seem to produce, in addition, any deleterious effects that would need to be compensated for to get the maximum growth performing effect from the agents,” McClellan said.
McClellan says that the information learned from the study may shed light on studies of neural regeneration in mammals, including perhaps humans.
“In mammals, cyclic AMP does appear to enhance regeneration within the central nervous system in an environment that is normally inhibitory for regeneration. So it seems to be able to overcome some of these inhibitory factors and promote at least some regeneration,” McClellan said. “Hopefully our studies with the lamprey can provide a list of conditions that are important for neural regeneration and that can guide therapies in higher vertebrates, and possibly in humans.”
Contributors to the study, titled “Cyclic AMP stimulates neurite outgrowth of lamprey reticulospinal neurons without substantially altering their biophysical properties,” include first author Timothy Pale and Emily Frisch, MU Division of Biological Sciences. The study was funded by the National Institutes of Health, the University of Missouri (MU) Spinal Cord Injury Program, UM Research Board, and MU Research Council.
Written by: Melody Kroll
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