Lessons learnt from the lamprey about spinal cord regeneration
You could be forgiven for never having heard of the lamprey, an obscure lineage of fish that shared a common ancestor with humans approximately 550 million years ago.
In fact, the only prominent example of this strange creature featuring in popular culture is their alleged role in the death of King Henry I, who, legend has it, met a gruesome demise after gorging himself on a “surfeit of lampreys.” Disappointingly, historians now believe he simply died of food poisoning.
The ancient creature looks deceptively like an eel, though depictions often focus on its alarming circular mouth: a flat disk covered in menacing rings of teeth that the lamprey uses to latch onto their unfortunate prey and suck their blood. Primitive and somewhat creepy though they may appear, lampreys possess one nifty talent that has inspired great interest among scientists: the ability to regenerate their spinal cord.
In recent weeks this humble fish has been thrust into the spotlight once again, as researchers at the Marine Biology laboratory in Chicago have shown that the lamprey can spontaneously regenerate this critical structure not just once, as previously thought, but twice. “We’ve determined that central nervous system (CNS) regeneration in lampreys is resilient and robust after multiple injuries. The regeneration is nearly identical to the first time, both anatomically and functionally,” said Jennifer Morgan, a senior author.
Though some parts of the human body can recover well after damage – the liver, the skin, and the inner lining of the gut for example – the central nervous system does not share this capacity, and the aim of improving recovery after spinal cord injury has made this an active area of research. Understanding at a molecular level how primitive vertebrates like the lamprey manage this kind of repetitive CNS regeneration could provide insight into whether cells in the human body possess the right “circuitry” for the task, and if so, how to activate it.
Information in the central nervous system is passed in the form of electrical pulses through long branch-like cells called motor neurons, which originate in the brain and relay instructions through their elongated stems down the spinal cord. Through observing the lamprey, the group have noticed that some of these neurons die in response to injury, while others survive. The researchers are now attempting to identify which molecular tools the successful neurons may be using. “We are beginning to isolate individual descending neurons and look at their transcriptional profiles (gene activity), to see if we can determine what makes some of them better at regenerating than others,” explains Morgan.
Work by Morgan’s group to elucidate the “molecular recipe” of regeneration has indicated that one particular group of genes, known as the “wnt pathway”, could be especially important to the process. This group of genes is also present in humans and is important for the development of different tissues within our organs.
Research from the University of Edinburgh in zebrafish, which can also regenerate the CNS, has also highlighted a role for the wnt genes. In these studies, researchers observed that wnt signals instructed cells to produce a molecule called collagen 12, which changes the structure that surrounds damaged nerve fibres at the site of injury, enabling their repair.
“In people and other mammals, the matrix in the injury site blocks nerves from growing back after an injury. We have now pinpointed the signals that remove this roadblock in zebrafish, so that nerve cells can repair connections that are lost after damage to the spinal cord” explained Dr Thomas Becker, who led this research.
Though we are coming closer to unravelling the molecular mechanism behind CNS regeneration, it is still not clear why several primitive vertebrates including the lamprey have retained this ability while humans have not. Some scientists believe that at one point CNS regeneration must have posed some kind of disadvantage for our ancestors, causing them to lose this capacity through natural selection. It is possible, for example, that the high complexity of the human brain may have made CNS regeneration more risky, as new nerve endings entering these highly organised networks were perhaps in danger of causing disruption and doing more harm than good – the nervous-system equivalent of blindly inserting new wires to a vastly complex and strictly regulated circuit.
There is still much work to be done before CNS regeneration becomes a possibility in humans, and even before we fully understand why we might have lost this ability over time. Research like that of Dr Jennifer Morgan hopes to improve current strategies for treatment by learning what we can from intriguing organisms like the all-too-often overlooked lamprey.
Image credit: Michael via Flickr