What is neurotoxin and where does it come from?
Neurotoxin is the collective term for toxins that attack the nervous system. However, the structure and the mechanism by which the toxins affect nerve cells varies greatly within this class. Neurotoxins can be anything from small organic molecules to larger proteins. A common feature for these molecules is their interference with the nervous system, preventing communication between nerve cells. This can lead to brain damage, developmental disability or paralysis because the brain loses communication with the muscles. In the worst case scenario, the paralysis can affect the respiratory muscles, resulting in death by suffocation.
Cyanobacteria, also known as blue-green algae, can be found in lakes and coastal areas during the summer (Figure 6A). The Cyanobacteria make the water green and murky, but they also produce various toxins. The toxins formed by blue-green algae are collectively called cyanotoxins. These small organic molecules have a range of toxicity mechanisms. Two of these toxins are highly effective at attacking the nervous system (neurotoxins). These two toxins are anatoxin-a, also known as Very Fast Death Factor, and saxitoxin, which was investigated as a potential chemical weapon by the CIA until it became illegal to manufacture or acquire under the UN Weapons Convention. These toxins prevent nerve cells from communicating properly with each other by binding on the surface of nerve cells, to receptors or ion channels respectively. Because of the cyanotoxins, it can be extremely dangerous to bath in water infected with blue-green algae, and therefore the growth of these Cyanobacteria is closely monitored by health authorities.
Neurotoxins are also found in the plant kingdom and (Figure 6A), plant neurotoxins are often based on small organic molecules, like the Cyanobacteria . The plant-neurotoxins are found in many different species, including the Nightshade family and the Umbellifer family. For example the poisonous plant hemlock is in the Umbellifer family (Figure 6B). Poison hemlock produces the toxic molecule coniin, which binds to a receptor on nerve cells. If hemlock is ingested, symptoms such as visual impairment, muscle fatigue and paralysis occur quickly. Hemlock originates from Mediterranean countries, but it is very versatile and has become an invasive species in many countries. It can now be found in most parts of the world. This creates a major problem, especially for grazing livestock such as cows, horses and sheep, as hemlock is toxic to all mammals.
But why do bacteria, plants and animals produce neurotoxins in the first place? In all cases, the reason is to improve their chances of survival in the wild. But how the neurotoxins are used to serve this purpose is very different. Plants, such as hemlock, use their poison as a means of defense to make it less attractive for herbivores to eat them. In the previous section, we presented an animal that has a similar defense mechanism, the poison dart frog. The mechanism can also be found in other animals, such as pufferfish. Pufferfish have a peculiar defense mechanism of inflating like a water balloon, pufferfish and hedgehogfish also contain one of the most potent neurotoxins. This neurotoxin, tetrodotoxin, is produced by symbiotic bacteria living in the fish and works by blocking ion channels on the nerve cell. Tetrodotoxin is extremely toxic (Table 1). Since there is no antidote, poisoning can lead to death within hours. Tetrodotoxin is what makes the Japanese delicacy Fugu extra exciting. Actually, it is a matter of life or death, as there is a risk of being poisoned if the fish is not cooked to perfection.
In addition to using neurotoxins as a defense mechanism, several animals have developed neurotoxins that can be used as a weapon to capture prey. For snakes, neurotoxins are an extremely useful weapon, as prey is often paralyzed after just one bite. This ensures, that the snakes only need contact with their prey for a shortly, minimizing the risk of injury during the hunt.
Another group of animals that utilize potent neurotoxins to capture prey are cone snails. These slow snails feed on fast small fish, which may sound like an impossible task. To successfully catch their fast prey, the snails are equipped with a small harpoon that can be fired at high speed over short distances. When the fish are speared by the harpoon, they are injected with a potent neurotoxin consisting of several different “conotoxins” (from name “conesnails”). The conotoxins paralyze the fish almost instantly and the snail can then slowly retrieve the harpoon and the meal is secured. You can watch a video clip of the phenomenon here.
Where and how does neurotoxin affect the body?
As mentioned earlier, neurotoxins affect nerve cells, but the way the nerve cells are affected varies greatly depending for different neurotoxins. There are three main mechanisms that neurotoxins apply to attack nerve cells (Figure 7): 1) By binding to ion channels and blocking their function. 2) By binding to ion pumps and blocking their function. 3) By creating holes in the cell membrane of the nerve cell, allowing ions to freely diffuse in and out, rendering the nerve cell unable to send electrical signals.