Just Keep Swimming: A Tail of Zebrafish Regeneration
The human brain is arguably the most complex organ. Throughout life, it is shaped ever so slightly by each and every experience we endure. The resulting nuances are what make us unique individuals. Unfortunately, the more intricate the system, the harder it is to fix when damaged. Death of any brain tissue will almost certainly result in some sort of physical or cognitive impairment, and, in severe cases, epilepsy, coma, or death. This is because the lost brain tissue can neither grow back like skin nor be replaced like a kidney.
Or can it?
While a brain transplant is still pure science fiction, news of the first planned human head transplant by Dr. Sergio Canavero has gained media attention in recent years. Assuming a patient is healthy above the neck, the head could – in theory – be transplanted to the body of a recently deceased donor. The procedure involves decapitation followed by reattaching various components of the neck, including blood vessels that supply oxygen to the brain, the esophagus and trachea so the patient can eat and breathe, and the spinal cord so the patient can hopefully gain control of the donor body.
Even if the surgery goes smoothly and no immune rejection occurs, the human central nervous system is notoriously difficult to heal. This is largely because severed nerve axons are prone to scarring and degeneration. Even Superman actor Christopher Reeve, after suffering a cervical injury that did not completely sever the spinal cord, could not regain motor control of his own body below the neck in the nine years following injury until his death in 2004.
Since then, scientists have been working hard to decipher the mechanisms of regeneration following spinal cord injury, and tackling questions such as, “Can therapeutics help a completely severed spinal cord reconnect?” and “Can motor and sensory control be regained following reconnection?”
“The human central nervous system is notoriously difficult to heal.”
One model organism of particular interest to the regeneration field is the zebrafish, which are able to fully regenerate a variety of injured tissues including the spinal cord.
A paper recently published in Science shows just how astounding the zebrafish’s regenerative capacity really is. Following complete severing of the spinal cord in wild type fish, Dr. Mayssa Mokalled and colleagues at Duke University and the Max Planck Institute showed that the two halves are able to bridge together and reconnect after about two weeks with restoration of swimming ability.
Furthermore, the researchers showed that expression of protein connective tissue growth factor a (ctgfa) is necessary for bridging the gap between severed axons. Without this protein, a condition scientists call “knock out,” the spinal cord cannot reconnect. With more of this protein, a condition scientists call “overexpression,” the spinal cord reconnects even faster. Using these principles, swimming ability can be more quickly restored with extra ctgfa.
Identification of ctgfa and other proteins that are necessary for enhancing regeneration is a major goal of fundamental science research. Once we understand how the process works, then we can figure out how to make it happen better and faster and eventually facilitate use of these technologies in humans.
“It is clear that in the years following Superman’s accident, science has made enormous strides in understanding the mechanisms underlying neural regeneration.”
However, we are still a long way off, and there are many differences between zebrafish and humans that need to be further examined. Most notably, the size and complexity of the human nervous system far exceeds that of the zebrafish. While a zebrafish may only need to move its tail left and right for swimming, human movement is much more complex. Moreover, we do not yet know if sensation can be restored along with motor function in such a transplant. After all, being able to move a leg is hardly useful if one cannot feel the position of the leg as straight or bent, in the air or on the ground.
It is clear that in the years following Superman’s accident, science has made enormous strides in understanding the mechanisms underlying neural regeneration. However, there remains much more to be understood. In the face of adversity, we must push forward with research and just keep swimming…
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Image by Jooyeun Lee.
References:
Mokalled, M. H., Patra, C., Dickson, A. L., Endo, T., Stainier, D. Y., & Poss, K. D. (2016). Injury-induced ctgfa directs glial bridging and spinal cord regeneration in zebrafish. Science, 354(6312), 630-634.
