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Paralysis, Memory and Learning:
Do Our Bodies Hold the Promise of Regeneration?
by Kumar Narayanan
Every year, television advertising during the Super Bowl serves as a pointer to what Americans are thinking about. One of the more memorable ads from this year's game featured a computer-generated version of actor Christopher Reeve rising unsteadily from his seat and walking across a stage, to the thunderous applause of the audience. The ad tugs at public compassion for Reeve's tragic story, shown to us through an avalanche of images over the last decade: early photographs of Reeve, handsome and strong, the actor we all knew as the original Superman; recent photographs of Reeve, calm and determined, and paralyzed from the neck down by a severe spinal cord injury. What the ad suggests is that the seemingly impossible computer-generated dream - Reeve's recovery from spinal paralysis - might be made possible by scientific research. Recent studies characterizing a group of proteins called neurotrophins suggest that there may be good reason for such hope.
Spinal cord injury is difficult to treat because when spinal neurons are injured or killed, it is difficult to induce them to recover. When we are very young children our bodies are filled with neurons that grow and change, actively shaping the connections between the brain and body. As we mature, the pattern of connections in our nervous system acquires a greater degree of stability, helping us to refine and perfect our muscular control. But if we suffer from a traumatic injury as an adult, the neural stability that helps us refine our control over our bodies becomes a barrier for recovery. In order to heal injured neurons, scientists must figure out what helps neurons grow and change in very young bodies, and how to reactivate those mechanisms to help grown-up bodies recover from neural injury.
Early Insights
The scientific journey from the molecules that shape the developing nervous system to potential therapies for neural injury follows an interesting path, starting, oddly enough, from a series of Argentinian experiments on snake venom. In 1956, biologist Rita Levi-Montalcini and her American collaborator Victor Hamburger reported that snake venom could induce the tremendous and rapid growth of mouse spinal cord neurons. Somewhere in the stew of chemicals that made up snake venom lurked a promising "nerve growth factor," a compound that held tremendous potential for therapy and research. Through the hard work of Levi-Montalcini and her colleagues, that factor was eventually purified and characterized. Today, Nerve Growth Factor (NGF) is the archetype of a whole family of neurotrophins, proteins in the nervous system that help regulate neural development and function.
Figure 1. Neurotrophins can induce growth in neurons
Neurotrophins help many neurons to survive and grow. In this example, the neurotrophin dramatically increases the number and length of the neuron's dendrites. More dendrites might allow the neuron to make additional connections with other neurons, and that type of change may underlie nerve repair as well as some types of learning and memory.
In the half century since the work that initially characterized NGF, the range of its potential applications has only broadened. The earliest studies demonstrated that neurotrophins are driving forces in most aspects of neural development, and more recent studies suggest that neurotrophins might also play a role in the types of neural rewiring associated with learning and memory. Harnessing the power of neurotrophins would provide vast therapeutic prospects for treating spinal cord damage and a whole host of neurodegenerative diseases such as Alzheimer's or Lou Gehrig's disease. Perhaps the greatest promise of neurotrophic factors lies in their potential to enhance our ability to learn and to remember.
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