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Neurotoxins

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 25:13351345.

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.

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neurotoxin

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.

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neurotoxin

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

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neurotoxin

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

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Neurotoxin

Neurotoxin


Neurotoxins are a special class of metabolic poisons that attack nerve cells. Disruption of the nervous system as a result of exposure to neurotoxins is usually quick and destructive. Neurotoxins are categorized according to the nature of their impact on the nervous system. Anesthetics (ether, chloroform, halothane), chlorinated hydrocarbons (DDT, Dieldrin, Aldrin), and heavy metals (lead , mercury ) disrupt the ion transport across cell membranes essential for nerve action. Common pesticides, including carbamates such as Sevin, Zeneb and Maneb and the organophosphates such as Malathion and Parathion, inhibit acetylcholinesterase, an enzyme that regulates nerve signal transmission between nerve cells and the organs and tissues they innervate.

Environmental exposure to neurotoxins can occur through a variety of mechanisms. These include improper use, improper storage or disposal, occupational use, and accidental spills during distribution or application. Since the identification and ramifications of all neurotoxins are not fully known, there is risk of exposure associated with this lack of knowledge.

Cell damage associated with the introduction of neurotoxins occurs through direct contact with the chemical or a loss of oxygen to the cell. This results in damage to cellular components, especially in those required for the synthesis of protein and other cell components.

The symptoms associated with pesticide poisoning include eye and skin irritation, miosis, blurred vision, headache, anorexia, nausea, vomiting, increased sweating, increased salivation, diarrhea, abdominal pain, slight bradycardia, ataxia, muscle weakness and twitching, and generalized weakness of respiratory muscles. Symptoms associated with poisoning of the central nervous system include giddiness, anxiety, insomnia, drowsiness, difficulty concentrating, poor recall, confusion, slurred speech, convulsions, coma with the absence of reflexes, depression of respiratory and circulatory centers, and fall in blood pressure.

The link between environmental neurotoxin exposure and neuromuscular and brain dysfunction has recently been identified. Physiological symptoms of Alzheimer's disease, amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), and lathyrism have been identified in populations exposed to substances containing known neurotoxins. For example studies have shown that heroin addicts who used synthetic heroin contaminated with methylphenyltetrahydropyridine developed a condition which manifests symptoms identical to those associated with Parkinson disease. On the island of Guam, the natives who incorporate the seeds of the false sago plant (Cycas circinalis ) into their diet develop a condition very similar to ALS. The development of this condition has been associated with the specific nonprotein amino acid , B methylamino-1-alanine, present in the seeds.

[Brian R. Barthel ]


RESOURCES

BOOKS


Aldrich, T., and J. Griffith. Environmental Epidemiology. New York: Van Nostrand Reinhold, 1993.

PERIODICALS

Griffith, J., R.C. Duncan, and J. Konefal. "Pesticide Poisonings Reported By Florida Citrus Field Workers." Environmental Science and Health 6 (1985): 70127.

OTHER

Agency for Toxic Substances and Disease Registry, Annual Report 1989 and 1990. Atlanta, GA: U.S. Department of Health and Human Services.

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