Posts tagged neurotoxins
Articles and news from the latest research reports.
Grasshopper Mice Are Numb to the Pain of the Bark Scorpion Sting
The painful, potentially deadly stings of bark scorpions are nothing more than a slight nuisance to grasshopper mice, which voraciously kill and consume their prey with ease. When stung, the mice briefly lick their paws and move in again for the kill.
The grasshopper mice are essentially numb to the pain, scientists have found, because the scorpion toxin acts as an analgesic rather than a pain stimulant.
The scientists published their research this week in Science.
Ashlee Rowe, lead author of the paper, previously discovered that grasshopper mice, which are native to the southwestern United States, are generally resistant to the bark scorpion toxin, which can kill other animals.
It is still unknown why the toxin is not lethal to the mice.
“This venom kills other mammals of similar size,” said Rowe, Michigan State University assistant professor of neuroscience and zoology. “The grasshopper mouse has developed the evolutionary equivalent of martial arts to use the scorpions’ greatest strength against them.”
Rowe, who conducted the research while at The University of Texas at Austin, and her colleagues ventured into the desert and collected scorpions and mice for their experiments.
To test whether the grasshopper mice felt pain from the toxin, the scientists injected small amounts of scorpion venom or nontoxic saline solution in the mice’s paws. Surprisingly, the mice licked their paws (a typical toxin response) much less when injected with the scorpion toxin than when injected with a nontoxic saline solution.
“This seemed completely ridiculous,” said Harold Zakon, professor of neuroscience at The University of Texas at Austin. “One would think that the venom would at least cause a little more pain than the saline solution. This would mean that perhaps the toxin plays a role as an analgesic. This seemed very far out, but we wanted to test it anyway.”
Rowe and Zakon discovered that the bark scorpion toxin acts as an analgesic by binding to sodium channels in the mouse pain neurons, and this blocks the neuron from firing a pain signal to the brain.
Pain neurons have a couple of different sodium channels, called 1.7 and 1.8, and research has shown that when toxins bind to 1.7 channels, the channels open, sodium flows in and the pain neuron fires.
By sequencing the genes for both the 1.7 and 1.8 sodium channels, the scientists discovered that channel 1.8 in the grasshopper mice has amino acids different from mammals that are sensitive to bark scorpion stings, such as house mice, rats and humans. They then found that the scorpion toxin binds to one of these amino acids to block the activation of channel 1.8 and thus inhibit the pain response.
“Incredibly, there is one amino acid substitution that can totally alter the behavior of the toxin and block the channel,” said Zakon.
The riddle hasn’t been completely solved just yet, though, Rowe said.
“We know the region of the channel where this is taking place and the amino acids involved,” she said. “But there’s something else that’s playing a role, and that’s what I’m focusing on next.”
Some resistance to prey toxins in mammals has been found in other species. The mongoose, for example, is resistant to the cobra. And naked mole rats’ eyes do not burn in pain when carbon dioxide builds up in their underground tunnels.
This study, however, is the first to find that an amino acid substitution in sodium channel 1.8 can have an analgesic effect.
Rowe said studies such as this could someday help researchers target these sodium channels for the development of analgesic medications for humans.
Brain may flush out toxins during sleep
NIH-funded study suggests sleep clears brain of molecules associated with neurodegeneration
A good night’s rest may literally clear the mind. Using mice, researchers showed for the first time that the space between brain cells may increase during sleep, allowing the brain to flush out toxins that build up during waking hours. These results suggest a new role for sleep in health and disease. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the NIH.
“Sleep changes the cellular structure of the brain. It appears to be a completely different state,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center in New York, and a leader of the study.
For centuries, scientists and philosophers have wondered why people sleep and how it affects the brain. Only recently have scientists shown that sleep is important for storing memories. In this study, Dr. Nedergaard and her colleagues unexpectedly found that sleep may be also be the period when the brain cleanses itself of toxic molecules.
Their results, published in Science, show that during sleep a “plumbing” system, called the glymphatic system, may open, letting fluid flow rapidly through brain. Dr. Nedergaard’s lab recently discovered the glymphatic system helps control whether cerebrospinal fluid (CSF), a clear liquid surrounding the brain and spinal cord, flows through the brain.
“It’s as if Dr. Nedergaard and her colleagues have uncovered a network of hidden caves and these exciting results highlight the potential importance of the network in normal brain function,” said Roderick Corriveau, Ph.D., a program director at NINDS.
Initially the researchers studied the system by injecting dye into the CSF of mice and watching it flow through their brains while simultaneously monitoring electrical brain activity. The dye flowed rapidly when the mice were unconscious, either asleep or anesthetized. In contrast, the dye barely flowed when the same mice were awake.
“We were surprised by how little flow there was into the brain when the mice were awake,” said Dr. Nedergaard. “It suggested that the space between brain cells changed greatly between conscious and unconscious states.”
To test this idea, the researchers inserted electrodes into the brain to directly measure the space between brain cells. They found that the space inside the brains increased by 60 percent when the mice were asleep or anesthetized.
“These are some dramatic changes in extracellular space,” said Charles Nicholson, Ph.D., a professor at New York University’s Langone Medical Center and an expert in measuring the dynamics of brain fluid flow and how it influences nerve cell communication.
Certain brain cells, called glia, control flow through the glymphatic system by shrinking or swelling. Noradrenaline is an arousing hormone that is also known to control cell volume. Treating awake mice with drugs that block noradrenaline induced sleep and increased brain fluid flow and the space between cells, further supporting the link between the glymphatic system and sleep.
Previous studies suggest that toxic molecules involved in neurodegenerative disorders accumulate in the space between brain cells. In this study, the researchers tested whether the glymphatic system controls this by injecting mice with radiolabeled beta-amyloid, a protein associated with Alzheimer’s disease, and measuring how long it lasted in their brains when they were asleep or awake. Beta-amyloid disappeared faster in mice brains when the mice were asleep, suggesting sleep normally clears toxic molecules from the brain.
“These results may have broad implications for multiple neurological disorders,” said Jim Koenig, Ph.D., a program director at NINDS. “This means the cells regulating the glymphatic system may be new targets for treating a range of disorders.”
The results may also highlight the importance of sleep.
“We need sleep. It cleans up the brain,” said Dr. Nedergaard.
(Source: ninds.nih.gov)