Two Howard Hughes Medical Institute research teams working independently have discovered new information about how the botulinum neurotoxin shuts down neurons with deadly efficiency. By providing detailed views of the toxin plugged into its neuronal receptor, the new studies could aid efforts to engineer specialized versions of the powerful neurotoxin that is used to treat a wide array of medical problems. The two groups were led by HHMI investigators Axel Brunger at Stanford University and Edwin Chapman at the University of Wisconsin at Madison. They published their findings December 13, 2006, in advance online publications in the journal Nature. "Botulinum neurotoxins are powerful tools for biologists and find widespread use as therapeutics for the treatment of certain nervous-system diseases," wrote Giampietro Schiavo of the London Research Institute in an accompanying News & Views commentary in Nature. "For these reasons, the papers reported here are of tremendous value." Botulinum neurotoxins are among the most deadly natural toxins in the world. They act by first attaching themselves to receptors on the surface of neurons. The toxins then insinuate an enzyme into the neuron that degrades key proteins required for neurons to communicate with one another. The toxins principally affect muscle-controlling motor neurons activated by the neurotransmitter acetylcholine. They kill by paralyzing the respiratory muscles. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), called serotypes A through G, with each acting in a slightly different manner.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 9747 - Posted: 12.14.2006

The regions in robins' brains responsible for singing and mating are shrinking when exposed to high levels of DDT, says new University of Alberta research--the first proof that natural exposure to a contaminant damages the brain of a wild animal. "These residues have been persisting since the late 1960s--that's what is really disturbing," said Dr. Andrew Iwaniuk, a post-doctoral research fellow in the U of A's Department of Psychology. "It has been years since it has been used and still has this effect." The new research, published in Behavioural Brain Research, strongly suggests that exposure to environmental levels of DDT causes significant changes in the brains of songbirds. Previous studies have suggested that exposure to DDT residues affect the brain, but none have actually demonstrated it. The research team, including Iwaniuk's supervisor, psychology professor and Tier II Canada Research Chair Douglas Wong-Wylie, used American Robins to test the idea. Birds are more susceptible to the effects of pesticide residues and other contaminants in the environment than other animals. As well, American robins are often exposed to high levels of DDT and other chemicals because they rely heavily on earthworms as part of their diet. They specifically chose these birds in the Okanagan Valley because at that location they are exposed to high levels of DDT, but relatively low levels of other chemicals.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology; Chapter 12: Sex: Evolutionary, Hormonal, and Neural Bases
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology; Chapter 8: Hormones and Sex
Link ID: 9137 - Posted: 07.15.2006

By JANE E. BRODY There's no question that the amount of lead in children's blood has dropped significantly in recent decades, much to the benefit of their brains and bodies. There's also no question that children who are still being permanently damaged by excessive lead levels live mainly at the poverty level or near it, in neighborhoods where they can be poisoned by lead from contaminated paint, water, soil and dust. More Personal Health Columns However, no one at any level of society, not even those with seven-figure incomes, can afford to be complacent about the exposure of children to lead in home and play environments. Here are some disturbing facts important to everyone concerned about the damage lead can cause and its individual and societal costs. About a quarter of the nation's children are exposed to lead at home, and more than 400,000 children are found each year to harbor amounts of lead deemed hazardous to normal mental and physical development. Environmental exposure to lead in early childhood is a prelude to a host of societal ills. It is associated with an increased risk of reading problems, school failure, delinquency and criminal behavior. Copyright 2006 The New York Times Company

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 4: Development of the Brain; Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 8416 - Posted: 01.19.2006

UCLA scientists have discovered how chronic exposure to low levels of carbon monoxide (CO) damages the inner ear of young rats, resulting in permanent hearing loss. At the Ca/OSHA's exposure limit of 0.0025 percent -- or 25 parts per million CO in the air -- the gas creates oxidative stress, a condition that damages the cochlear cells, leading to impairment of the auditory nerves. Tobacco smoke, gas heaters, stoves and ovens all emit CO, which can rise to high concentrations in poorly ventilated homes. Infants and children are particularly vulnerable to CO exposure because they spend a great deal of time in the home. No policies exist to regulate CO in the home. Many commercial home monitors sound an alarm only 20 minutes after CO concentrations reaches 70 parts per million -- nearly three times the 25 parts per million limit set by Cal/OSHA. This is the first time that inhaled CO has been linked to oxidative stress, a known risk factor in many disorders, including Alzheimer's, Parkinson's, multiple sclerosis, Lou Gherig's disease and cardiovascular disease. Tobacco smoke, which contains CO, aggravates many of these diseases. The UCLA findings highlight the need for policy makers to reexamine the regulation of car exhaust, tobacco smoke, smog, and heating and cooking appliances.

Related chapters from BN: Chapter 9: Hearing, Balance, Taste, and Smell
Related chapters from MM:Chapter 6: Hearing, Balance, Taste, and Smell
Link ID: 7447 - Posted: 06.04.2005

New research shows that farmers who used agricultural insecticides experienced increased neurological symptoms, even when they were no longer using the products. Data from 18,782 North Carolina and Iowa farmers linked use of insecticides, including organophosphates and organochlorines, to reports of reoccurring headaches, fatigue, insomnia, dizziness, nausea, hand tremors, numbness and other neurological symptoms. Some of the insecticides addressed by the study are still on the market, but some, including DDT, have been banned or restricted. These findings will be available online in April, and published in the June issue of Environmental Health Perspectives. The research is part of the ongoing Agricultural Health Study funded by the National Institute of Environmental Health Sciences and the National Cancer Institute, two of the National Institutes of Health, and the Environmental Protection Agency. "This research is really important because it evaluated the health effects of agricultural chemicals as they were commonly used by farmers. It's different from previous studies that focused on pesticide poisoning or high dose exposures, for example when large amounts of a chemical were accidentally spilled on the skin," said Freya Kamel, Ph.D., a researcher for the National Institute of Environmental Health Sciences (NIEHS). The NIEHS researchers examined questionnaires completed by farmers on lifetime exposure to herbicides, insecticides, fungicides, and fumigants, and their history of 23 neurological symptoms. Those who reported experiencing more than 10 symptoms during the year prior to completing a study questionnaire were classified as having high levels of symptoms.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 7270 - Posted: 04.29.2005

By CARL ZIMMER The inland taipan, a nine-foot-long Australian snake, is not the sort of creature most people would want to bother. Drop for drop, its venom is the deadliest in the world, 50 times as potent as cobra venom. Its fangs are so long they can poke through the snake's lower jaw. Its victims collapse in seconds and suffer a quick death. Dr. Bryan Fry, a biologist from the University of Melbourne, will readily admit he is not like most people. He not only bothers inland taipans; he hunts them down in dense cane fields, pins them down and bags them. Later he grabs them by the head and squeezes venom from their fangs. Besides inland taipans, Dr. Fry collects venom from death adders, rattlesnakes, king cobras, sea snakes and many others. He estimates that he handles 2,000 to 3,000 snakes a year. "Working with some of these snakes is the biggest adrenaline rush you could ever do," he admitted. "I used to do extreme ski jumping and big wave surfing, but none of that can touch working with some of these animals." Copyright 2005 The New York Times Company

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 7144 - Posted: 04.05.2005

Every year, millions of people try to look younger by taking injections of Botox, a prescription drug that gets rid of facial wrinkles by temporarily paralyzing muscles in the forehead. Although best known as a cosmetic procedure, Botox injections also have been approved by the Food and Drug Administration (FDA) to treat uncontrolled blinking (blepharospasm), lazy eye (strabismus), involuntary muscle contractions in the neck (cervical dystonia) and acute underarm sweating (severe primary axillary hyperhidrosis). Botox users might be surprised to learn that they're actually receiving minute injections of a bacterial neurotoxin called botulinum, one of the most poisonous substances known. Exposure to large amounts of botulinum bacteria can cause a paralytic, sometimes-fatal disease called botulism. Last month, several Floridians were hospitalized with botulism after receiving injections of an anti-wrinkle treatment that authorities suspect was a cheap, non-FDA-approved imitation of Botox. The botulinum toxin works by invading nerve cells, where it releases an enzyme that prevents muscle contraction. In recent years, scientists have determined that the enzyme binds to specific sites on proteins called SNAREs, which form a complex in the synapse between nerve and muscle cells. Without SNAREs, nerves cannot release the chemical signals that tell muscle cells to contract, and paralysis results.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 6581 - Posted: 12.14.2004

The illnesses suffered by veterans of the first Gulf War appeared to be linked to toxins including nerve gas, according to a US report. The US Veterans Affairs Department said stress or mental illness did not explain most veterans' complaints, but there was a probable link to toxins. British campaigners are demanding the government recognise "Gulf War Syndrome". The UK's Ministry of Defence (MoD) says there is not enough evidence to prove its existence. The report, by the Research Advisory Committee on Gulf War Veterans' Illnesses, said up to 30% of US Gulf War veterans had been afflicted by a "complex of multiple chronic symptoms over and above expected rates seen in veterans who did not serve in the Gulf War". "A growing body of research indicates that an important component of Gulf War veterans' illnesses is neurological in character. It added: "Evidence supports a probable link between exposure to neurotoxins and the development of Gulf War veterans' illnesses." It found veterans had developed Lou Gehrig's disease at about twice the rate of veterans who did not serve in the Gulf War. Symptoms include headaches, memory problems, confusion, dizziness, blurred vision and tremors. It said reports indicated a large number of Gulf War troops were exposed to a variety of potentially toxic substances, including low levels of chemical nerve agents, pills taken to protect veterans from the effects of nerve agents and insect repellents and pesticides, that can adversely affect the nervous system. The Pentagon has previously acknowledged that some troops may have been exposed to the nerve agent sarin when Iraqi munitions were destroyed. The MoD said it was aware of most of the material in the report. (C)BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 6416 - Posted: 11.13.2004

By SCOTT SHANE The government will spend $15 million over the next year for research on the illnesses of veterans of the 1991 Persian Gulf war, the secretary of veterans affairs, Anthony J. Principi, announced Friday. He said it would concentrate on the role of neurotoxins, and not the stress and psychological conditions often implicated as a cause of the veterans' health complaints. Mr. Principi also said the department would establish a research center to develop treatments for gulf war illnesses. "The men and women who fought there deserve our undivided attention to their questions, to their symptoms, to their futures," he said. "They have been frustrated far too long." He said his decision was guided by the findings of a committee of scientists and veterans that he appointed in 2002 to study the ailments of thousands of servicemen and women that persisted after the war. In a report released at a news conference here, the panel, the Research Advisory Committee on Gulf War Veterans' Illnesses, broke with earlier study groups by pointing to chemical exposures during the war, not the effects of combat stress, as the primary cause of what has sometimes been called Gulf War Syndrome. Copyright 2004 The New York Times Company

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 6415 - Posted: 11.13.2004

Gulf war syndrome may have been caused by exposure to the nerve gas sarin, according to reports. The New Scientist journal has reported a leak of a US inquiry into the ill-health of veterans of the 1991 war. The US Department of Veterans Affairs' Research Advisory Committee on Gulf War Veterans' Illnesses is due to publish its findings next week. But the magazine said researchers have found neural damage consistent with the nerve agent used by Saddam Hussein. The link is said to have been "crucial" to a change of heart by the US authorities over Gulf war syndrome. The New York Times newspaper reported last month that US scientists believed the syndrome did exist and was caused by "toxic exposure" but it was not clear whether this was from drugs or nerve agents. The UK government has always insisted a unique Gulf war syndrome does not exist. But campaigners say 6,000 British war veterans are suffering from the syndrome, with symptoms ranging from mood swings, memory loss, lack of concentration, night sweats, general fatigue and sexual problems since the war. According to the New Scientist report "a substantial proportion of Gulf war veterans are ill with multi-system conditions not explained by wartime stress or psychiatric illness". Instead, the magazine reported the ill-health could have been caused by low level exposure to sarin. Three research groups had independently found specific kinds of neural damage that could explain some of the veterans' symptoms. (C)BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 6370 - Posted: 11.04.2004

By SCOTT SHANE WASHINGTON, - A federal panel of medical experts studying illnesses among veterans of the 1991 war in the Persian Gulf has broken with several earlier studies and concluded that many suffer from neurological damage caused by exposure to toxic chemicals, rejecting past findings that the ailments resulted mostly from wartime stress. Citing new scientific research on the effects of exposure to low levels of neurotoxins, the Research Advisory Committee on Gulf War Veterans' Illnesses concludes in its draft report that "a substantial proportion of Gulf War veterans are ill with multisymptom conditions not explained by wartime stress or psychiatric illness." It says a growing body of research suggests that many veterans' symptoms have a neurological cause and that there is a "probable link" to exposure to neurotoxins. The report says possible sources include sarin, a nerve gas, from an Iraqi weapons depot blown up by American forces in 1991; a drug, pyridostigmine bromide, given to troops to protect against nerve gas; and pesticides used to protect soldiers in the region. Copyright 2004 The New York Times Company

Related chapters from BN: Chapter 3: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Related chapters from MM:Chapter 2: Neurophysiology: The Generation, Transmission, and Integration of Neural Signals
Link ID: 6248 - Posted: 10.15.2004

Last year a remarkable exhibit came to light. Hidden in the vaults of a London museum was a scrap of paper containing a few strands of hair. The paper was crudely fashioned into an envelope but the words on it immediately caused a stir: "Hair of His Late Majesty, King George 3rd." For Professor Martin Warren, it was the clue that would help him finally solve the mystery of King George's illness. His investigation is featured in a BBC documentary, Medical Mysteries. "King George is largely remembered for those periods when he lost his mind. But it's been difficult to explain these attacks, so I was keen to analyse this hair sample," said Professor Warren. When the hair was tested by the Harwell International Business Centre for Science & Technology in Didcot, Oxfordshire, the results were surprising. The king's hair was laden with arsenic. It contained over 300 times the toxic level. "This level is way above anything we were expecting - it's taken us completely by surprise." Far from being an answer, this remarkable finding was just the start of Warren's detective work. In King George's time, his bizarre behaviour and wild outbursts were treated as insanity. He was bound in a straight-jacket and chained to a chair to control his ravings. King George was officially mad. It wasn't until the 1970s that a new and controversial diagnosis was made. Two psychiatrists - Ida MacAlpine and her son Richard Hunter - revisited the king's medical records and noticed a key symptom; dark red urine - a classic and unmistakable sign of a rare blood disorder called porphyria. Porphyria can be a devastating disease. In the acute form, it can cause severe abdominal pain, cramps, and even seizure-like epileptic fits. (C)BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 5808 - Posted: 07.14.2004

By Paul Rincon Molecules that destroy deadly nerve agents could provide the basis of a new type of civilian drug to protect people against a terrorist attack. The US army is testing the enzymes - called paraoxonases - to see if they could be used to protect troops from exposure during battle. But Israeli researchers working in the field say any new drug could also have a role in the civil defence setting. However, the new technology is likely to take some years to develop and test. The paraoxonases might also have applications as sprays to decontaminate areas and groups of people exposed to nerve agents. Paraoxonases are a particularly attractive choice as the basis for developing pre-treatment drugs, or prophylactics, because they completely break down organophosphorus nerve agents like sarin, the agent used in the Tokyo underground attack in March 1995. (C)BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 5395 - Posted: 05.03.2004

By KIRK JOHNSON The number of severe lead poisoning cases among children has sharply declined in New York City over the last 20 years as old peeling paint has been removed from apartments and homes. But thousands of children tested each year still have lead levels in their blood high enough to raise health concerns. At least part of the reason, city health officials and other experts say, may be the broader environment of the city itself: lead that is in the soil, on the streets and underneath dozens of miles of elevated subway, where the steel support structures were painted for decades with lead-based paint. Peeling and chipping indoor lead paint is almost certainly the prime threat to small children, who can eat the paint or breathe its dust, health experts agree. Copyright 2003 The New York Times Company

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 4464 - Posted: 11.02.2003

By JOHN NOBLE WILFORD Mighty as Hercules was, he sometimes prevailed only by means other than his own brute strength. When the need arose, the superhero of Greek mythology armed himself with biochemical weaponry, anticipating the technological innovations of modern warfare. Up against the Many-Headed Hydra, Hercules forced the monstrous serpent from its den by shooting fiery arrows coated with pitch. After finally slaying the Hydra, he cut open the body and dipped his arrows in its poisonous venom. His quiver was never again without a supply of poison arrows. The story of Hercules and the Hydra may be the first description in Western literature of chemical and biological weapons. Because myth often contains a kernel of historical reality, the story suggests that projectiles tipped with combustible or toxic substances must have been known early in Greek history, and widely used in combat. Copyright 2003 The New York Times Company

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 4344 - Posted: 10.07.2003

ITHACA, N.Y. -- A five-year study has found that lead is harmful to children at concentrations in the blood that are typically considered safe. Reporting in the latest issue (April 17) of The New England Journal of Medicine , two Cornell University scientists say that children suffer intellectual impairment at a blood-lead concentration below the level of 10 micrograms per deciliter (mcg/dl) -- about 100 parts per billion -- currently considered acceptable by the Centers for Disease Control and Prevention (CDC). "We also found that the amount of impairment attributed to lead was most pronounced at lower levels," says Richard Canfield, lead author of the journal paper and a senior researcher in Cornell's Division of Nutritional Sciences. The study followed 172 children in the Rochester, N.Y., area whose blood lead was assessed at 6, 12, 18, 24, 36, 48 and 60 months and who were tested for IQ at both 3 and 5 years of age. The study was conducted by researchers at Cornell, the Cincinnati Children's Hospital, the University of Rochester, the National Institutes of Health and the University of Washington.

Related chapters from BN: Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 4: Development of the Brain
Link ID: 3700 - Posted: 04.17.2003

Drugs to protect against a nerve-gas attack are a distant goal A possible "achilles heel" for chemical weapons has been found. Scientists have discovered how organophosphate chemicals act on nerves, raising new possibilities for developing antidotes. The research adds weight to the argument that genetics may play a role in human susceptibility to organophosphates. The class of chemicals includes household pesticides as well as deadly nerve gases like sarin. Experiments in mice show organophosphate nerve agents target a key enzyme. Genetically-altered rodents with low levels of the enzyme were more sensitive to the chemical. The mice were more likely to die or show symptoms such as hyperactivity when exposed to high doses of organophosphates. (C) BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 3581 - Posted: 03.19.2003

A new first-aid method of treating carbon monoxide poisoning could prevent brain damage in patients by delivering more oxygen to the brain than the standard treatment, according to a study by physicians at the Toronto General Hospital, University Health Network (UHN). The study is published in the December issue of the U.S. based and peer-reviewed journal Annals of Emergency Medicine. The researchers, led by Dr. Josh Rucker, a Toronto General Hospital research fellow and resident in the Anesthesiology training program at the University of Toronto, studied 14 subjects who were exposed to low levels of carbon monoxide (resulting in blood levels about equal to those in heavy smokers) on two occasions in order to simulate conditions during carbon monoxide poisoning.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 3108 - Posted: 12.04.2002

Scientists have stumbled on a secret weapon against snails and slugs. They have discovered the garden pests are poisoned by caffeine. A strong cup of coffee is enough to send the creatures into a writhing frenzy, followed soon by death. Scientists think caffeine acts as a potent neurotoxin against the pests. The finding may be of use to gardeners and commercial growers. Slugs and snails are notoriously difficult to deter from attacking plants. The chemicals currently used to control them are not permitted as residues on food crops. (C) BBC

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 2287 - Posted: 07.07.2002

DURHAM, N.C. -- A Duke University Medical Center pharmacologist is recommending caution when using the insecticide DEET, after his animal studies last year found the chemical causes diffuse brain cell death and behavioral changes in rats after frequent and prolonged use. Mohamed Abou-Donia, Ph.D. has also called for further government testing of the chemical's safety in short-term and occasional use, especially in view of Health Canada's recent decision to ban products with more than 30 percent of the chemical. Every year, approximately one-third of the U.S. population uses insect repellents containing DEET, available in more than 230 products with concentrations up to 100 percent. While the chemical's risks to humans are still being intensely debated, Abou-Donia says his 30 years of research on pesticides' brain effects clearly indicate the need for caution among the general public.

Related chapters from BN: Chapter 4: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Related chapters from MM:Chapter 3: The Chemistry of Behavior: Neurotransmitters and Neuropharmacology
Link ID: 1990 - Posted: 05.02.2002