Posts tagged neuropeptides
Articles and news from the latest research reports.
Beneath the Surface: What Zebrafish Can Tell Us About Anxiety
The right tool for the job is important. A surgeon wouldn’t use a chainsaw when a scalpel offers more control. But sometimes the best treatments available aren’t precise. For example, anxiety medications available today are too blunt in how they target the brain, according to Ian Woods, assistant professor of biochemistry at Ithaca College.
“If you look at current treatments for anxiety disorders, the approach is a bit like taking a sledgehammer to a mosquito,” he said. “The treatments may work for anxiety, but they can have a lot of side effects.”
Woods researches how genetics influence responses to stimuli that can trigger anxiety, and he’s using zebrafish — a tropical member of the minnow family named for the black stripes on their bodies — to do so. He and his team of student researchers examine how fish with tweaked genes respond to different triggers compared to unmodified fish. The work could someday lead to better, more nuanced medications for anxiety disorders.
Zebrafish make ideal test subjects for several reasons. The embryos are transparent and develop outside the mother’s body, making it easy for Woods and his team to observe their growth under a microscope. They develop rapidly, are easy to care for and easy to breed in large quantities.
Specifically, Woods is looking at neuropeptides, which are the chemical messengers between brain cells. Different neuropeptides deliver different messages, which in turn produce different behaviors.
“Fish have the same neuropeptides as humans, and they mostly do the same things in the brain,” Woods said. “We can never faithfully model a complex human behavior like anxiety, but when we’re trying to figure out how the brain works, it’s useful to see inside a fish.”
Woods and his team isolate specific genes to disrupt, amplify, alter or replace, then analyze the movements of the modified fish with the aid of a computerized camera system. They examine responses to stimuli such as slight changes in water temperature, decreases in light intensity, or mild chemical irritants such as mustard oil.
“By observing the ensuing behavioral changes in the fish, we know how that replaced gene changed the message in the brain,” Woods explained. For example, fish exhibiting anxiety-like behaviors might hug the walls of the tank, while the rest will swim toward the middle. It’s not unlike social experiments in which the room temperature is raised gradually to see how human occupants will react.
“Genes typically don’t cause the anxiety,” Woods said. “But they can make organisms more susceptible to environmental triggers that might elicit what we’d call an anxious behavior.”
Anxiety disorders are the most common mental illness in the United States; over 40 million Americans suffer from some type in their lifetimes. But medications can be overprescribed and abused. For example, emergency room visits related to the use of Xanax and related drugs doubled from 2005 to 2011, according to the U.S. Substance Abuse and Mental Health Services Administration.
Neurons Can Use Local Stores for Communication Needs
Researchers reveal that neurons can utilize a supremely localized internal store of calcium to initiate the secretion of neuropeptides, one class of signaling molecules through which neurons communicate with each other and with other cells. The study appears in The Journal of General Physiology.
(Image caption: Localization of ryanodine receptors (red) in an isolated nerve terminal from the posterior pituitary gland. Image credit: McNally et al., 2014)
Neuropeptides are released from neurons through a process that—like other secretory events—is triggered primarily by the influx of calcium into the neuron through voltage-gated channels. Although neuropeptides are stored in large dense core vesicles (LDCVs) that also contain large amounts of calcium, it has been unclear whether these locally based calcium supplies can also be used to modulate secretion.
A team of researchers led by José Lemos from the University of Massachusetts Medical School examined the mechanisms at play during secretion of vasopressin from nerve terminals in the posterior pituitary gland, which releases the neuropeptide into the blood so that it can make its way to the kidney and regulate water retention. The researchers found that certain intracellular calcium channels known as ryanodine receptors are likely responsible for mobilizing calcium from LDCVs to facilitate vasopressin release. The findings indicate that neurons have a greater capacity than previously appreciated to fine-tune the release of neuropeptides and thereby their communications with other cells.
(Source: newswise.com)
Scientists link honeybees’ changing roles throughout their lives to brain chemistry
Scientists have been linking an increasing range of behaviors and inclinations from monogamy to addiction to animals’, including humans’, underlying biology. To that growing list, they’re adding division of labor — at least in killer bees. A report published in ACS’ Journal of Proteome Research presents new data that link the amounts of certain neuropeptides in these notorious bees’ brains with their jobs inside and outside the hive.
Mario Sergio Palma and colleagues explain that dividing tasks among individuals in a group is a key development in social behavior among Hymenoptera insects, which include bees, ants, sawflies and wasps. One of the starkest examples of this division of labor is the development of “castes,” which, through nutrition and hormones, results in long-lived queens that lay all the thousands of eggs in a colony and barren workers that forage for food and protect the hive. Bee researchers had already observed that honeybees, including Africanized Apis mellifera, better known as “killer” bees, divide tasks by age. As workers get older, their roles change from nursing and cleaning the hive to guarding and foraging. Palma’s team wanted to see whether peptides in the brain were associated with the bees’ shifting duties.
They found that the amounts of two substances varied by time and location in the brains of the honeybees in a way that mirrored the timing of their changing roles. “Thus, these neuropeptides appear to have some functions in the honeybee brain that are specifically related to the age-related division of labor,” the scientists conclude.
(Source: acs.org)
Researchers Pinpoint Protein Crucial For Development Of Biological Rhythms In Mice
Johns Hopkins researchers report that they have identified a protein essential to the formation of the tiny brain region in mice that coordinates sleep-wake cycles and other so-called circadian rhythms.
(Image caption: An illustration of the activity patterns of normal mice (left). An illustration of the activity patterns mice whose “master clock,” or SCN, has been disrupted (right). Credit: Cell Reports, Bedont et al.)
By disabling the gene for that key protein in test animals, the scientists were able to home in on the mechanism by which that brain region, known as the suprachiasmatic nucleus or SCN, becomes the body’s master clock while the embryo is developing.
The results of their experiments, reported in the tk issue of Cell Reports, are an important step toward understanding how to better manage the disruptive effects experienced by shift workers, as well as treatment of people with sleep disorders, the researchers say.
“Shift workers tend to have higher rates of diabetes, obesity, depression and cancer. Many researchers think that’s somehow connected to their irregular circadian rhythms, and thus to the SCN,” says Seth Blackshaw, Ph.D., an associate professor in the Department of Neuroscience and the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. “Our new research will help us and other researchers isolate the specific impacts of the SCN on mammalian health.”
Blackshaw explains that every cell in the body has its own “clock” that regulates aspects such as its rate of energy use. The SCN is the master clock that synchronizes these individual timekeepers so that, for example, people feel sleepy at night and alert during the day, are hungry at mealtimes, and are prepared for the energy influx that hits fat cells after eating. “A unique property of the SCN is that if its cells are grown in a dish, they quickly synchronize their clocks with each another,” Blackshaw says.
But while evidence like this gave researchers an idea of the SCN’s importance, they hadn’t completely teased its role apart from that of the body’s other clocks, or from other parts of the brain.
The Johns Hopkins team looked for ways to knock down SCN function by targeting and disabling certain genes that disrupt only the formation of the SCN clock. They analyzed which genes were active in different areas of developing mouse brains to identify those that were “turned on” only in the SCN. One of the “hits” was Lhx1, a member of a family of genes whose protein products affect development by controlling the activity of other genes. When the researchers turned off Lhx1 in the SCN of mouse embryos, the grown mice lacked distinctive biochemical signatures seen in the SCN of normal mice.
The genetically modified mice behaved differently, too. Some fell into a pattern of two to three separate cycles of sleep and activity per day, in contrast to the single daily cycle found in normal mice, while others’ rhythms were completely disorganized, Blackshaw says. Though an SCN is present in mutant mice, it communicates poorly with clocks elsewhere in the body.
Blackshaw says he expects that the mutant mice will prove a useful tool in finding whether disrupted signaling from the SCN actually leads to the health problems that shift workers experience, and if so, how this might happen. Although mouse models do not correlate fully to human disease, their biochemical and genetic makeup is closely aligned.
Blackshaw’s team also plans to continue studying the biochemical chain of events surrounding the Lhx1 protein to determine which proteins turn the Lhx1 gene on and which genes it, in turn, directly switches on or off. Those genes could be at the root of inherited sleep disorders, Blackshaw says, and the proteins they make could prove useful as starting points for the development of new drugs to treat insomnia and even jet lag.
Insulin plays a role in mediating worms’ perceptions and behaviors
Using salt-sniffing roundworms, Salk scientists help explain how the nervous system processes sensory information
In the past few years, as imaging tools and techniques have improved, scientists have been working tirelessly to build a detailed map of neural connections in the human brain—with the ultimate hope of understanding how the mind works.
But determining how cells in the brain are physically connected is only the first clue for decoding our perceptions and behaviors. We also need to know the precise routes that information takes in the brain in a given context. Now, publishing their results September 8, 2013, in the journal Nature Neuroscience, researchers at the Salk Institute for Biological Studies have shown a striking example of the flexibility in neural circuitry and its influence on behaviors in worms, depending on the animals’ environment.
The roundworm Caenorhabditis elegans has exactly 302 neurons—far less than the estimated 100 billion neurons a person has—and we already know how each of them is connected. That, in addition to how easily the tiny creature’s cells can be manipulated, allows researchers to ask what sort of information passes through the circuits—in molecular-and circuit-level detail—and what are the behavioral consequences of this information flow.
Even with a comprehensive map of the worm’s neuronal connections in hand, however, scientists still don’t know how the animal can interact with its environment in thousands of different ways. That’s one big question that Sreekanth Chalasani, an assistant professor in Salk’s Molecular Neurobiology Laboratory and Sarah Leinwand, a doctoral student at the University of California, San Diego, sought to answer.
In C. elegans, thanks to studies performed more than 20 years ago, many sensory neurons were identified to have distinct roles such as sensing temperature, pheromones, salt and odors. To know what these cells did, scientists had zapped them one-by-one with a laser and measured the worms’ behaviors. These studies implicated one neuron in the detection of increased salt in the worm’s surroundings.
In the new study, rather than ablating individual sensory neurons, Leinwand and Chalasani imaged worms that expressed genetically encoded calcium indicators in their neurons, which caused the cells to light up when active. Surprisingly, after exposure to an attractive but high concentration of salt, the worms’ olfactory sensory neuron lit up.
"We were extremely surprised to see that with these new tools, these new calcium sensors, we could discover that there was more than one type of neuron involved in processing sensory cues that people had thought were only sensed by single neurons," says Leinwand.
Using additional genetic manipulations and behavioral assays, the researchers showed that the olfactory neuron—while still important for sensing odorants—was crucial for the worm’s movement toward salt within a certain concentration range. Unexpectedly, this neuron’s response to salt also required the previously identified salt-sensing neuron. In fact, the olfactory neuron was not directly sensing salt but instead was being activated by the salt sensory neuron, they found.
What information was the salt-sensing neuron sending to the olfactory neuron? Neurons communicate with each other by sending chemical and electrical signals through close contacts with their neighbors. By testing worms whose signaling molecules had been genetically knocked out, Chalasani and Leinwand could see which were playing a role in transmission when the worm was stimulated by higher salt. From these experiments, they saw that a neuropeptide, a small protein present in neurons, was being released by the salt-sensing neuron to shape the animal’s behavior.
Identifying the neuropeptide (or neuropeptides) responsible for the context-dependent signaling was the most challenging part of the study, because the worm has 115 genes that code for some 250 neuropeptides, Chalasani says. Luckily, there are only four different molecular machines that process all of these peptides; by using genetic knockouts of each of the four, Leinwand and Chalasani were quickly able to narrow the list down to about 40 genes which coded for insulin neuropeptides.
One by one, the team tracked olfactory neuron responses to high salt in worms missing each gene, finding that worms lacking the gene for an insulin neuropeptide known as INS-6 did not respond to increases in salt. Putting this peptide back restored the animal’s normal responses to high salt.
"It was rewarding to see that, while there might be more than one peptide signal, the contributions from INS-6 are certainly significant," Leinwand says. She and Chalasani also found the specific receptor on the receiving end of the olfactory neurons.
That insulin was the main signaling molecule recruiting the olfactory neuron into a salt-sensing circuit was a big surprise.
"Traditionally, neuropeptides have been thought to modulate neuronal function over many seconds to many minutes," Chalasani says. "But in this particular instance, it looks like the insulin is acting in less than a second to transfer information from the salt-sensing neuron to the neuron which normally responds to odor."
Similar neuropeptide communication may also create flexible neural circuits that mediate the diverse behaviors that other animals and people perform in their environments. Insulin has many roles in people—it has been implicated in aging and metabolism, for example—but so far it has only been shown to function on a slower, minute time-scale.
Chalasani and Leinwand plan to investigate whether there are other fast neural circuit switches in worms—and if so, whether those switches act through neuropeptide signaling or some other mechanism. They’re also interested in how the circuit switch changes as the animal ages. “You would expect that as the animal is aging, some of this communication becomes less efficient,” Chalasani says.
Researchers identify brain pathway triggering impulsive eating
New research from the University of Georgia has identified the neural pathways in an insect brain tied to eating for pleasure, a discovery that sheds light on mirror impulsive eating pathways in the human brain.
"We know when insects are hungry, they eat more, become aggressive and are willing to do more work to get the food," said Ping Shen, a UGA associate professor of cellular biology in the Franklin College of Arts and Sciences. "Little is known about the other half-the reward-driven feeding behavior-when the animal is not so hungry but they still get excited about food when they smell something great.
The fact that a relatively lower animal, a fly larva, actually does this impulsive feeding based on a rewarding cue was a surprise.”
The research team led by Shen, who also is a member of the Biomedical and Health Sciences Institute, found that presenting fed fruit fly larvae with appetizing odors caused impulsive feeding of sugar-rich foods. The findings, published Feb. 28 in Cell Press, suggest eating for pleasure is an ancient behavior and that fly larvae can be used in studying neurobiology and the evolution of olfactory reward-driven impulses.
To test reward-driven behaviors in flies, Shen introduced appetizing odors to groups of well-fed larvae. In every case, the fed larvae consumed about 30 percent more food when surrounded by the attractive odors.
But when the insects were offered a substandard meal, they refused to eat it.
"They have expectations," he said. "If we reduce the concentration of sugar below a threshold, they do not respond anymore. Similar to what you see in humans, if you approach a beautiful piece of cake and you taste it and determine it is old and horrible, you are no longer interested."
Shen’s team also tried to further define this phenomenon-the connection between excitement and expectation. He found when the larvae were presented with a brief odor, the amount of time they were willing to act on the impulse was about 15 minutes.
"After 15 minutes, they revert back to normal. You get excited, but you can’t stay excited forever, so there is a mechanism to shut it down," he said.
His work also suggests the neuropeptides, or brain chemicals acting as signaling molecules triggering impulsive eating, are consistent between flies and humans. Neurons receive and convert stimuli into thoughts that are then relayed to the downstream mechanism telling the animals to act. These signaling molecules are required for this impulse, suggesting the molecular details of these functions are evolutionarily tied between flies and humans.
"There are hyper-rewarding cues that humans and flies have evolved to perceive, and they connect this perception with behavior performance," Shen said. "As long as this is activated, the animal will eat food. In this way, the brain is stupid: It does not know how it gets activated. In this case, the fly says ‘I smell something, I want to do this.’ This kind of connection has been established very early on, probably before the divergence of fly and human. That is why we both have it."
Impulsive and reward-driven behaviors are largely misunderstood, partially due to the complex systems at work in human brains. Fly larvae nervous systems, in terms of scheme and organization, are very similar to adult flies and to mammals, but with fewer neurons and less complex wirings.
"A particular function in the brain of mammals may require a large cluster of neurons," he said. "In flies, it may be only one or four. They are simpler in number but not principle."
In the fly model, four neurons are responsible for relaying signals from the olfactory center to the brain to stimulate action. Each odor and receptor translates the response slightly differently. Human triggers are obviously more diverse, but Shen thinks the mechanism to appreciate the combination is likely the same. He is now working with Tianming Liu, assistant professor of computer science at UGA and member of the Bioimaging Research Center and Institute of Bioinformatics, on a computer model to determine how these odors are interpreted as stimuli.
"Dieting is difficult, especially in the environment of these beautiful foods," Shen said. "It is very hard to control this impulsive urge. So, if we understand how this compulsive eating behavior comes about, we maybe can devise a way, at least for the behavioral aspect, to prevent it. We can modulate our behaviors better or use chemical interventions to calm down these cues."
Neurotransmitters Linked to Mating Behavior Are Shared by Mammals and Worms
When it comes to sex, animals of all shapes and sizes tend to behave in predictable ways. There may be a chemical reason for that. New research from Rockefeller University has shown that chemicals in the brain — neuropeptides known as vasopressin and oxytocin — play a role in coordinating mating and reproductive behavior in animals ranging from humans to fish to invertebrates.
"Our research shows that molecules similar to vasopressin and oxytocin have an ancient and evolutionarily conserved role in controlling a critical social behavior, mating," says Cori Bargmann, Torsten N. Wiesel Professor and head of the Lulu and Anthony Wang Laboratory of Neural Circuits and Behavior. "This work suggests that these molecules encode the same kind of information in the brains of very different animals."
Bargmann, whose laboratory studies the relationship between genes, neural circuits and behavior in the C. elegans roundworm, says vasopressin and oxytocin have been implicated in a variety of reproductive and social behaviors in humans and other mammals, including pair bonding, maternal bonding and aggressive and affiliative behaviors. Mice that lack oxytocin may develop social amnesia, and humans who sniff oxytocin through an inhaler change their cooperative behavior in computer games, behaving as though they “trust” other players more.