Traveling Toxin: Botox may hitch a ride on nerve cells

Botox can make your face muscles stay put, but it may not stay put in your face. Evidence from experiments with rodents suggests that the neurotoxin can cruise along nerve cells and remain active beyond the injection site.

BOTOX ON THE GO. Known for their muscle-relaxing action, botulinum toxins are used therapeutically. But they are able to migrate from an injection site, probably via nerve cells. iStockphoto

Understanding the mechanisms and pathways that toxins use is “of fundamental importance,” comments Giampietro Schiavo, of Cancer Research UK in London, who studies a related toxin that causes tetanus and also travels in the body via nerve cells.

Botox is actually a trade name for one of several toxins that target nerve cells and are made by the rod-shaped bacterium Clostridium botulinum. While extremely poisonous in the wrong dose—the neurotoxins have been developed as biological weapons and cause the sometimes-lethal illness botulism—the toxins are also used therapeutically. And not just for erasing wrinkles. The toxins can help calm hyperactive muscles that accompany many disorders, including Parkinson’s disease and multiple sclerosis.

The new findings “should not deter any physicians, nor should patients be discouraged,” says J. Oliver Dolly, director of the International Centre for Neurotherapeutics at Dublin City University in Ireland, who adds that the toxin is important for treating many diseases. “From a basic science point of view, this has more relevance for studying the transport of proteins.”

Botulinum toxins act by interfering with nerve-muscle communication. When a nerve cell wants a muscle to contract, the nerve sends the order via the chemical messenger known as acetylcholine. Botulinum toxins slice up proteins that are in charge of passing the acetylcholine message to muscle fibers. Since they never get the memo, the muscles relax and sit tight. The effects can last from days to months, depending on the toxin used.

In the new study, scientists tracked two botulinum toxins by looking for the sliced up proteins that the toxins leave in their wake. Led by Matteo Caleo of Italy’s National Research Institute (CNR) in Pisa, the researchers injected a botulinum toxin into each rodent’s superior colliculus, a part of the brain that deals with input from the eye. Three days later, sliced up protein appeared in the retina, suggesting that the toxin traveled and moved opposite the direction of nerve signals, the researchers report in the April 2 Journal of Neuroscience.

The team also injected botulinum toxins into the rodents’ whisker pads and found evidence that the toxins had traveled to the part of the brain stem that controls muscles used for facial expression. When toxin was injected into one side of the hippocampus, it traveled to the other side, dampening the activity of nerves in both areas.

The depression of nerve activity in the untreated side of the hippocampus “was a real surprise,” says Caleo, adding that clinicians have assumed that the toxins’ action is localized and restricted. Because the cleaved protein always turned up in nerve populations directly connected to the injection site, the toxins likely travel within the nerve cell.

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