Neurotoxins

Many chemical compounds, some natural and some made by humans, show toxic effects in humans or other animals. Every toxin is harmful, but toxins that target the nervous system have been developed into chemical warfare agents, so the public concern about them is enhanced.

Despite the connection with weapons of mass destruction, the most common neurotoxin in society is ethanol, found in alcoholic beverages. Neurons convey signals by manipulating ion concentrations, and neurotoxins reduce their ability to do so. Alcohol does this by essentially overloading the entire cell and hindering its ability to function. Many of the characteristics of alcohol intoxication, such as slurred speech and erratic motion, are the result of improper function of neurons in the brain. As the body metabolizes the alcohol and removes it from the blood, the neurotoxic effects wear off. With large overdoses of alcohol, however, the effects do not wear off, and death due to alcohol poisoning is a dramatic and unfortunately too common manifestation of neurotoxins.

The neurotoxins that are associated with chemical warfare typically operate in a different fashion. A neuron carries a signal as a miniature electric current. Ions carry charges, and when they move across the cell membrane in a specific region of a neuron at a rapid rate they change the electrical potential in that region. The rapid movement of ions migrates along the neuron and propagates an electrical signal (called an action potential ). When this signal reaches the end of the neuron, it must somehow trigger a response in the next neuron. In a few cases, neurons are packed closely enough so that the charge associated with the moving action potential directly excites the next neuron. In most cases, the first neuron releases small molecules called neurotransmitters that diffuse across a small gap (the synaptic cleft ) and interact with the next neuron, triggering its response. Many neurotoxins, including both human-made agents of chemical warfare and natural agents found in venoms and other natural toxins, work by disrupting this communication process.

There are two common mechanisms by which nerve signaling is disrupted. The cell that receives the signal does so when receptors within its membrane interact with the neurotransmitters. Some neurotoxins act by blocking these receptors, making it impossible for them to receive signals. When signaling stops, nerve function is impaired or eliminated and, the neurotoxin has caused its damage.

The other key component of interneuron communication is that the neurotransmitters, once they have carried a signal across a synaptic cleft, must be removed. If a "receiving" neuron is continually stimulated because neurotransmitters continue to activate it, the neuron's function will be impaired, and the neuron may even be killed. There are special enzymes in the synaptic cleft that break down certain neurotransmitters, such as acetylcholine , to end the signaling. Some neurotoxins block the actions of these hydrolytic enzymes, thereby preventing the removal of acetylcholine (or other neurotransmitters), leading to continuous stimulation of the neurons and, ultimately, cell death.

see also Acetylcholine; Inhibitors; Neurotransmitters.

Thomas A. Holme

Bibliography

Changeux, Jean-Pierre; Devillers-Thiery, Anne; and Chemeuilli, Phillippe (1984). "The Acetylcholine Receptor: An Allosteric Protein." Science 25:1335–1345.

Crosby, Donald G. (1998). Environmental Toxicology and Chemistry. New York: Oxford University Press.

Simpson, Lance L. (1971). Neuropoisons: Their Pathophysiological Actions. New York: Plenum Press.

neurotoxin A chemical that either physically damages a nerve or reduces or alters the function of the nerve. An example of a neurotoxin is 6-hydroxydopamine, which damages the nerve terminals of the sympathetic neurons. This compound is structurally similar to dopamine and noradrenaline and can enter the nerve terminal by existing transport systems.

neurotoxin A toxin that affects the functioning of the nervous system.

neurotoxin A toxin that affects the functioning of the nervous system.