"It was like red-hot pokers needling one side of my face," says Catherine, recalling the cluster headaches she experienced for six years. "I just wanted it to stop." But it wouldn’t – none of the drugs she tried had any effect.

Thinking she had nothing to lose, last year she enrolled in a pilot study to test a handheld device that applies a bolt of electricity to the neck, stimulating the vagus nerve – the superhighway that connects the brain to many of the body’s organs, including the heart.

The results of the trial were presented last month at the International Headache Congress in Boston, and while the trial is small, the findings are positive. Of the 21 volunteers, 18 reported a reduction in the severity and frequency of their headaches, rating them, on average, 50 per cent less painful after using the device daily and whenever they felt a headache coming on.

This isn’t the first time vagal nerve stimulation has been used as a treatment – but it is one of the first that hasn’t required surgery. Some people with epilepsy have had a small generator that sends regular electrical signals to the vagus nerve implanted into their chest. Implanted devices have also been approved to treat depression. What’s more, there is increasing evidence that such stimulation could treat many more disorders from headaches to stroke and possibly Alzheimer’s disease.

The latest study suggests it is possible to stimulate the nerve through the skin, rather than resorting to surgery. “What we’ve done is figured out a way to stimulate the vagus nerve with a very similar signal, but non-invasively through the neck,” says Bruce Simon, vice-president of research at New Jersey-based ElectroCore, makers of the handheld device. “It’s a simpler, less invasive way to stimulate the nerve.”

Cluster headaches are thought to be triggered by the overactivation of brain cells involved in pain processing. The neurotransmitter glutamate, which excites brain cells, is a prime suspect. ElectroCore turned to the vagus nerve as previous studies had shown that stimulating it in people with epilepsy releases neurotransmitters that dampen brain activity.

When the firm used a smaller version of ElectroCore’s device on rats, it found it reduced glutamate levels and excitability in these pain centres. Other studies have shown that vagus nerve stimulation causes the release of inhibitory neurotransmitters which counter the effects of glutamate.

The big question is whether a non-implantable device can really trigger changes in brain chemistry in humans, or whether people are simply experiencing a placebo effect. “The vagus nerve is buried deep in the neck, and something that’s delivering currents through the skin can only go so deep,” says Mike Kilgard of the University of Texas at Dallas. As you turn up the voltage, there’s a risk of it activating muscle fibres that trigger painful cramps, he adds.

Simon says that volunteers using the device haven’t reported any serious side effects. He adds that ElectroCore will soon publish data showing changes in brain activity in humans after using the device. Placebo-controlled trials are also about to start.

Catherine has been using it for a year without ill effect. “I can now function properly as a human being again,” she says.

The many uses of the wonder nerve

Coma, irritable bowel syndrome, asthma and obesity are just some of the disparate conditions that vagus nerve stimulation may benefit and for which human trials are under way.

It might also help people with tinnitus. Although people with tinnitus complain of ringing in their ears, the problem actually arises because too many neurons fire in the auditory part of the brain when certain frequencies are heard.

Mike Kilgard of the University of Texas at Dallas reasoned that if people were played tones that didn’t trigger tinnitus while the vagus nerve was stimulated, this might coax the rogue neurons into firing in response to these frequencies instead. “By activating this nerve we can enhance the brain’s ability to rewire itself,” he says.

He has so far tested the method in rats and in 10 people with tinnitus, using an implanted device to stimulate the nerve. Not everyone noticed an improvement, but even so Kilgard is planning a larger trial. The work was presented at a meeting of the International Union of Physiological Sciences in Birmingham, UK, last month. The technique is also being tested in people who have had a stroke.

"If these studies stand up it could be worth changing the name of the vagus nerve to the wonder nerve," says Sunny Ogbonnaya at Cork University Hospital in Ireland.

Neuroscientists often use electroencephalography (EEG) as an inexpensive way to record electrical signals in the brain. Though it would be useful to run these recordings for long periods of time, that usually isn’t practical: EEG recording traditionally involves attaching many electrodes and cables to a patient’s scalp.

Now engineers at Imperial College in London have developed an EEG device that can be worn inside the ear, like a hearing aid. They say the device will allow scientists to record EEGs for several days at a time; this would allow doctors to monitor patients who have regularly recurring problems like seizures or microsleep.

“The ideal is to have a very stable recording system, and recordings which are repeatable,” explains co-creator Danilo Mandic. “It’s not interfering with your normal life, because there are acoustic vents so people can hear. After a while, they forget they’re having an EEG.”

By nestling the EEG inside the ear, the engineers avoid a lot of signal noise usually introduced by body movement. They can also ensure that the electrodes are always placed in exactly the same spot, which, they say, will make repeated readings more reliable.

Since the device attaches to just one area, it can record only from the temporal region. This limits its potential applications to events that involve local activity. Tzzy-Ping Jung, co-director of the University of California, San Diego’s Center for Advanced Neurological Engineering, says that this does not mean the device will not be valuable.

“Different modalities will have different applications. I would not rule out the usefulness of any modalities,” says Jung. “I think it’s a very good idea with very promising results.”

(Source: technologyreview.com)

From frogs to humans, selecting a mate is complicated. Females of many species judge suitors based on many indicators of health or parenting potential. But it can be difficult for males to produce multiple signals that demonstrate these qualities simultaneously.

In a study of gray tree frogs, a team of University of Minnesota researchers discovered that females prefer males whose calls reflect the ability to multitask effectively. In this species (Hyla chrysoscelis) males produce “trilled” mating calls that consist of a string of pulses.

Typical calls can range in duration from 20-40 pulses per call and occur between 5-15 calls per minute. Males face a trade-off between call duration and call rate, but females preferred calls that are longer and more frequent, which is no simple task.

The findings were published in August issue of Animal Behavior.

"It’s kind of like singing and dancing at the same time," says Jessica Ward, a postdoctoral researcher who is lead author for the study. Ward works in the laboratory of Mark Bee, a professor in the College of Biological Sciences’ Department of Ecology, Evolution and Behavior.

The study supports the multitasking hypothesis, which suggests that females prefer males who can do two or more hard-to-do things at the same time because these are especially good quality males, Ward says. The hypothesis, which explores how multiple signals produced by males influence female behavior, is a new area of interest in animal behavior research.

By listening to recordings of 1,000 calls, Ward and colleagues learned that males are indeed forced to trade off call duration and call rate. That is, males that produce relatively longer calls only do so at relatively slower rates.

"It’s easy to imagine that we humans might also prefer multitasking partners, such as someone who can successfully earn a good income, cook dinner, manage the finances and get the kids to soccer practice on time."

The study was carried out in connection with Bee’s research goal, which is understanding how female frogs are able to distinguish individual mating calls from a large chorus of males. By comparison, humans, especially as we age, lose the ability to distinguish individual voices in a crowd. This phenomenon, called the “cocktail party” problem, is often the first sign of a diminishing ability to hear. Understanding how frogs hear could lead to improved hearing aids.

(Source: www1.umn.edu)

A new study in Biological Psychiatry explores the influence of oxytocin

Difficulty in registering and responding to the facial expressions of other people is a hallmark of autism spectrum disorder (ASD). Relatedly, functional imaging studies have shown that individuals with ASD display altered brain activations when processing facial images.

The hormone oxytocin plays a vital role in the social interactions of both animals and humans. In fact, multiple studies conducted with healthy volunteers have provided evidence for beneficial effects of oxytocin in terms of increased trust, improved emotion recognition, and preference for social stimuli.

This combination of scientific work led German researchers to hypothesize about the influence of oxytocin in ASD. Dr. Gregor Domes, from the University of Freiburg and first author of the new study, explained: “In the present study, we were interested in the question of whether a single dose of oxytocin would change brain responses to social compared to non-social stimuli in individuals with autism spectrum disorder.”

They found that oxytocin did show an effect on social processing in the individuals with ASD, “suggesting that oxytocin may help to treat a basic brain function that goes awry in autism spectrum disorders,” commented Dr. John Krystal, Editor of Biological Psychiatry.

To conduct this study, they recruited fourteen individuals with ASD and fourteen control volunteers, all of whom completed a face- and house-matching task while undergoing imaging scans. Each participant completed this task and scanning procedure twice, once after receiving a nasal spray containing oxytocin and once after receiving a nasal spray containing placebo. The order of the sprays was randomized, and the tests were administered one week apart.

Using two sets of stimuli in the matching task, one of faces and one of houses, allowed the researchers to not only compare the effects of the oxytocin and placebo administrations, but also allowed them to discriminate findings between specific effects to only social stimuli and non-specific effects to more general brain processing.

What they found was intriguing. The data indicate that oxytocin specifically increases responses of the amygdala to social stimuli in individuals with ASD. The amygdala, the authors explain, “has been associated with processing of emotional stimuli, threat-related stimuli, face processing, and vigilance for salient stimuli”.

This finding suggests oxytocin might promote the salience of social stimuli in ASD. Increased salience of social stimuli might support behavioral training of social skills in ASD.

These data support the idea that oxytocin may be a promising approach in the treatment of ASD and could stimulate further research, even clinical trials, on the exploration of oxytocin as an add-on treatment for individuals with autism spectrum disorder.

(Source: alphagalileo.org)

The cells in our bodies can divide as often as once every 24 hours, creating a new, identical copy. DNA binding proteins called transcription factors are required for maintaining cell identity. They ensure that daughter cells have the same function as their mother cell, so that for example muscle cells can contract or pancreatic cells can produce insulin. However, each time a cell divides the specific binding pattern of the transcription factors is erased and has to be restored in both mother and daughter cells. Previously it was unknown how this process works, but now scientists at Karolinska Institutet have discovered the importance of particular protein rings encircling the DNA and how these function as the cell’s memory.

The DNA in human cells is translated into a multitude of proteins required for a cell to function. When, where and how proteins are expressed is determined by regulatory DNA sequences and a group of proteins, known as transcription factors, that bind to these DNA sequences. Each cell type can be distinguished based on its transcription factors, and a cell can in certain cases be directly converted from one type to another, simply by changing the expression of one or more transcription factors. It is critical that the pattern of transcription factor binding in the genome be maintained. During each cell division, the transcription factors are removed from DNA and must find their way back to the right spot after the cell has divided. Despite many years of intense research, no general mechanism has been discovered which would explain how this is achieved.

"The problem is that there is so much DNA in a cell that it would be impossible for the transcription factors to find their way back within a reasonable time frame. But now we have found a possible mechanism for how this cellular memory works, and how it helps the cell remember the order that existed before the cell divided, helping the transcription factors find their correct places", explains Jussi Taipale, professor at Karolinska Institutet and the University of Helsinki, and head of the research team behind the discovery.

The results are now being published in the scientific journal Cell. The research group has produced the most complete map yet of transcription factors in a cell. They found that a large protein complex called cohesin is positioned as a ring around the two DNA strands that are formed when a cell divides, marking virtually all the places on the DNA where transcription factors were bound. Cohesin encircles the DNA strand as a ring does around a piece of string, and the protein complexes that replicate DNA can pass through the ring without displacing it. Since the two new DNA strands are caught in the ring, only one cohesin is needed to mark the two, thereby helping the transcription factors to find their original binding region on both DNA strands.

"More research is needed before we can be sure, but so far all experiments support our model," says Martin Enge, assistant professor at Karolinska Institutet.

Transcription factors play a pivotal role in many illnesses, including cancer as well as many hereditary diseases. The discovery that virtually all regulatory DNA sequences bind to cohesin may also end up having more direct consequences for patients with cancer or hereditary diseases. Cohesin would function as an indicator of which DNA sequences might contain disease-causing mutations.

"Currently we analyse DNA sequences that are directly located in genes, which constitute about three per cent of the genome. However, most mutations that have been shown to cause cancer are located outside of genes. We cannot analyse these in a reliable manner - the genome is simply too large. By only analysing DNA sequences that bind to cohesin, roughly one per cent of the genome, it would allow us to analyse an individual’s mutations and make it much easier to conduct studies to identify novel harmful mutations," Martin Enge concludes.

(Source: ki.se)

The human body is a complicated system of blood vessels, nerves, organs, tissue and cells each with a specific job to do. When all are working together, it’s a symphony of form and function as each instrument plays its intended roles.

Biologist Rejji Kuruvilla and her fellow researchers uncovered what happens when one instrument is not playing its part.

Kuruvilla along with graduate students Philip Borden and Jessica Houtz, both from the Biology Department at Johns Hopkins University’s Krieger School of Arts and Sciences, and Dr. Steven Leach from the McKusick-Nathans Institute of Genetic Medicine at the Johns Hopkins School of Medicine, recently published a paper in the journal Cell Reports exploring whether “cross-talk” or reciprocal signaling, takes place between the neurons in the sympathetic nervous system and the tissues that the nerves connect to. In this case the targeted tissue called islets, were in the pancreas.

“We knew that sympathetic neurons need molecular signals from the tissues that they connect with, to grow and survive,” said Kuruvilla. “What we did not know was whether the neurons would reciprocally signal to the target tissues to instruct them to grow and mature. It made sense to focus on the pancreas because of previous studies done in diabetic animal models where sympathetic nerves within the pancreas were found to retract early on in the disease, suggesting that dysfunction of the nerves could be an early trigger for pancreatic defects.”

The researchers spent approximately three years working with lab mice to test the various scenarios in which signaling between sympathetic neurons and islet cells might take place. The experiments focused on what effects removing the sympathetic nerves would have on pancreas development in newborn mice.

Previous studies had shown that pancreatic cells release a signal of their own, a nerve growth protein, that directs the sympathetic nerves toward the pancreas and provides necessary nutrition to sustain the nerves.

In turn, Kuruvilla’s team found that in mutant mice, the removal of the sympathetic neurons resulted in deformities in the architecture of the pancreatic islet cells and defects in insulin secretion and glucose metabolism.

Pancreatic islets are highly organized functional micro-organs with a defined size, shape and distinctive arrangement of endocrine cells. It’s this marriage of form and function that result in cells clustered close together, that creates greater, more efficient islet cell function.

However, the mutant mice, with their sympathetic neurons removed, had islet formations that were misshapen, sported lesions and developed in a patchy, uneven manner. Because of their dysfunctional islet cell development, postnatal mice did not secrete enough insulin when confronted with high glucose, and had high blood glucose levels as a result. Increased levels of blood glucose in humans is a hallmark of diabetes.

It’s known in neuroscience that the neurons in question from the sympathetic nervous system control the body’s “flight or fight” response and communicate with connected tissues by releasing a chemical messenger called norepinephrine. The release of norepinephrine also plays an important role in the development and maturation of islets, said Kuruvilla.

Using sympathetic neurons and islet cells grown together in a culture dish, the researchers observed that islet cells move toward the nerves and identified norepinephrine as the nerve signal that causes the movement of the islet cells.

“Seeing how these islet cells were responding to sympathetic neurons both in a dish and the effects of removing the nerves in a whole animal on islet shape and functions were pretty remarkable,” said Borden, lead author of the paper. “It was clear to us that sympathetic neurons were key to how islets were developing, something no one else had shown.”

Kuruvilla said these studies, identifying sympathetic nerves as a critical player in organizing pancreatic cells during development and influencing their later function, could add to a better understanding of treating diabetes in the future. The research also lends support to the value in considering the importance of external factors such as nerves and blood vessels when transplanting islet cells for the treatment of diabetes in patients.

“This study reveals interactions between two co-developing systems, sympathetic neurons and pancreatic islet cells, that has important implications for peripheral organ development, and for regeneration of these tissues following injury or disease,” said Kuruvilla.

(Source: releases.jhu.edu)

New research at Rutgers University may help shed light on how and why nervous system changes occur and what causes some people to suffer from life-threatening anxiety disorders while others are better able to cope.

Maureen Barr, a professor in the Department of Genetics, and a team of researchers, found that the architectural structure of the six sensory brain cells in the roundworm, responsible for receiving information, undergo major changes and become much more elaborate when the worm is put into a high stress environment.

Scientists have known for some time that changes in the tree-like dendrite structures that connect neurons in the human brain and enable our thought processes to work properly can occur under extreme stress, alter brain cell development and result in anxiety disorders like depression and Post Traumatic Stress Disorder affecting millions of Americans each year.

What scientists don’t understand for sure, Barr says, is the cause behind these molecular changes in the brain.

“This type of research provides us necessary clues that ultimately could lead to the development of drugs to help those suffering with severe anxiety disorders,” Barr says.

In the study published today in Current Biology, scientists at Rutgers have identified six sensory nerve cells in the tiny, transparent roundworm, known as the C. elegans and an enzyme called KPC-1/furin which triggers a chemical reaction in humans that is needed for essential life functions like blood-clotting. 

While the enzyme also appears to play a role in the growth of tumors and the activation of several types of virus and diseases in humans, in the roundworm the enzyme enables its simple neurons to morph into new elaborately branched shapes when placed under adverse conditions.

Normally, this one-millimeter long worm develops from an embryo through four larval stages before molting into a reproductive adult. Put it under stressful conditions of overcrowding, starvation and high temperature and the worm transforms into an alternative larval stage known as the dauer that becomes so stress-resistant it can survive almost anything – including the Space Shuttle Columbia disaster in 2003 of which they were the only living things to survive.  

“These worms that normally have a short life cycle turn into super worms when they go into the dauer stage and can live for months, although they are no longer able to reproduce,” Barr says.

What is so interesting to Barr is that when a perceived threat is over, these tiny creatures and their IL2 neurons transform back to a normal lifespan and reproductive state like nothing had ever happened. Under a microscope, the complicated looking tree-like connectors that receive information are pruned back and the worm appears as it did before the trauma occurred.

This type of neural reaction differs in humans who can suffer from extreme anxiety months or even years after the traumatic event even though they are no longer in a threatening situation.   

The ultimate goal, Barr says, is to determine how and why the nervous system responds to stress. By identifying molecular pathways that regulate neuronal remodeling, scientists may apply this knowledge to develop future therapeutics.

(Source: news.rutgers.edu)