Alberta Innovates- Health Solutions

Recent advances in neuroscience offer hope to millions affected by brain, spinal cord, or peripheral nerve injuries or conditions. But as Heritage researcher Dr. Robert Campenot comments, "As we grow, the nerves grow with us without breaking connections. The notion of repair or re-growth of injured nerves in an adult means asking the nerves to do something they have never done before."

Before we advance our understanding enough to engineer repairs or cures of damaged nerves, Dr. Campenot believes we need more basic research. He has spent more than 25 years working in basic nerve research contributing some remarkable achievements to the field. As a post-doctoral fellow at Harvard, he worked with cultures of nerve cells, consisting of cell bodies and long filament-like axons, growing in the dish like a tangle of "spaghetti strands". If he could find a way to make the cell bodies grow their axons out to a different part of the dish, he could replicate the process by which axons find their targets in tissue.

Dr. Campenot tinkered with various devices and came up with a fluid-proof barrier across which the nerves could grow. His first experiment was with a protein known as a nerve growth factor necessary for the survival and growth of many types of nerve cells. He found that axons would grow only into regions of the dish supplied with nerve growth factor. By controlling the distribution of the nerve growth factor, he controlled where the nerve grew. This was a basic principle in neuroscience, but his invention of the "compartmented culture" provided the first tangible proof of it.

Now at the University of Alberta, Dr. Campenot continues to investigate nerve growth factors. "We know where they act in nerve cells and more about how their signalling works in nerve cells. So now we can study in more detail how signals travel from the growing tip and the terminals of an axon back to the nerve cell body."

When Dr. Campenot's lab applies nerve growth factor to axon terminals; it takes more than an hour before the transported protein begins to reach the cell body. Yet, the cell body receives notification of the nerve growth factor application in about 10 minutes by certain signalling proteins. Researchers at Johns Hopkins University and Harvard University are using Dr. Campenot's compartmentalized culture system to investigate this fast signalling system further.

Since nerve cells develop in very early life, why do nerve cells need growth factor to stay alive?

The nervous system produces about twice as many nerve cells as are needed in the early stages of life. The "left-over" neurons die. Nerve growth factor overrides the signals causing neuron death in those that remain. If Dr. Campenot can discover the fast signalling involved in the growth factor mechanism; he might keep neurons alive when diseases, such as Alzheimer's, kills them.

A basic problem with nerve regeneration is the growing axons need for "building" materials. These consist of proteins produced in the cell body and then transported down the axon to the growing tip. Lipid spheres called vesicles carry some faster materials. "However, the transportation can take a thousand days or longer to reach the growing tip. That may be too long to repair long axons. Not only that, but all sorts of degenerative changes occur in the tissue that has been without a nerve for that amount of time."

Dr. Campenot thinks the outside of the faster-moving vesicles carries these slow-moving proteins. They can jump on and off so travel slower than the vesicles carrying them. Finding ways to keep the proteins on the vesicles longer will speed up transport and aid in nerve regeneration and become a major contribution to the knowledge of the cell biology of the neuron.

Dr. Campenot has collaborated with Dr. Jean Vance and Heritage researcher, Dr. Dennis Vance and has shown that many membrane lipids (fats) develop in the growing axons and aren't dependent on supplies from the cell bodies. This contradicted the long-standing belief the cell bodies supply the membrane lipids and offers a new perspective on nerve regeneration.

Dr. Robert Campenot is a Heritage Medical Scientist at the University of Alberta who also receives funding from the Medical Research Council of Canada and the National Neurotrauma Fund. Members of Dr. Campenot's laboratory: Daren Ure, Donna Senger, and Dr. Hubert Eng, and Dr. Elena Posse de Chaves in Dr. Jean Vance's laboratory made major contributions to the above research.

For more information:
National Neurotrauma Society