New research might help people suffering from post-traumatic stress disorder

Saturday, 3 August 2013

Islamabad, Aug 4 (Newswire): The discovery of a mechanism in the brain explains for the first time why people make particularly strong, long-lasting memories of stressful events in their lives and could help sufferers of post-traumatic stress disorder.

The study, carried out by researchers from the University of Bristol's Henry Wellcome Laboratories for Integrative Neuroscience & Endocrinology (HW-LINE) in the School of Clinical Sciences, and funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is published in the Proceedings of the National Academy of Sciences (PNAS).

The research found that stress hormones directly stimulate biochemical processes in neurons that play a role in learning and memory. The way these hormones stimulate these signalling and epigenetic processes in neurons is completely new and has never been shown before.

In the healthy brain these processes operate smoothly and help people to cope with and learn from stressful events in their lives. In vulnerable people or in strongly traumatized people (victims of rape or war), these processes may be disturbed and stressful events may result in the formation of highly traumatic memories such as those seen in patients suffering from post-traumatic stress disorder (PTSD). The discovery may lead to new ways to develop drugs to help these patients and to prevent PTSD in trauma victims.

Professor Johannes Reul, Professorial Research Fellow in Neuroscience at HW-LINE, said: "Making memories of events in our lives is of critical importance in order to cope properly with new situations and challenges in the future. This is of particular importance for emotional and traumatic life events. Our newly discovered mechanism should be regarded as an adaptive mechanism. We believe this mechanism could be disturbed in stress-related psychiatric disorders such as depression and anxiety.

"The new findings may be of particular significance for patients suffering from post-traumatic stress disorder (PTSD) as these patients are pained by pathological memories of an endured trauma (rape or war situations). We hope our discovery may help to generate a new class of drugs to help these patients."

The researchers found that stress-induced glucocorticoid hormones enhance memory formation through a direct, physical interaction of glucocorticoid-binding receptors ("glucocorticoid receptor") with a particular intracellular signalling pathway in a specific population of neurons of the hippocampus. This signalling pathway, the so-called ERK MAPK pathway, is known to be strongly involved in learning and memory processes but it was not known that it could interact with glucocorticoid receptors and that this would lead to an enhancement of memory formation.

This type of interaction has never been described before. The interaction has a major impact as the stimulated signalling cascade results in augmented epigenetic mechanisms in the nucleus of the affected neurons leading to enhanced expression of certain gene products. The induced gene products are known to evoke structural and functional changes in neurons allowing them to strengthen their role in the memory circuits of the brain.

It is well known that people make very strong memories of stressful, emotionally disturbing events in their lives. These so-called episodic memories are memories of the place (e.g. room, office) or surroundings where the event happened, how we felt at the time (mood), and the time of the day at which it happened. These kind of memories can last a lifetime.

The consolidation of such memories is taking place in a specific limbic brain region called the hippocampus -- part of the brain involved in memory and learning. Hormones secreted during stress like the glucocorticoid hormone cortisol (in rodents, corticosterone) act on the hippocampus to enhance the consolidation of these memories. However, until now it has been unknown how these hormones act on the hippocampus to enhance the formation of emotional event-related memories.

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Artificial nanoparticles influence heart rate and rhythm

Islamabad, Aug 4 (Newswire): Artificial nanoparticles are becoming increasingly pervasive in modern life. However, their influence on our health and the mechanisms by which they affect the human body remain largely shrouded in mystery.

Using a so-called Langendorff heart, a team of scientists from the Technische Universitaet Muenchen (TUM) and the Helmholtz Zentrum Muenchen has now for the first time shown that selected artificial nanoparticles have a direct effect on heart rate and heart rhythm.

The scientists are presenting their results in the journal ACS Nano.

In light of the increasing demand for artificial nanoparticles in medicine and industry, it is important for manufacturers to understand just how these particles influence bodily functions and which mechanisms are at play -- questions to which there has been a dearth of knowledge. Studies on heart patients have shown for decades that particulate matter has a negative effect on the cardiovascular system.

Yet, it remained unclear whether the nanoparticles do their damage directly or indirectly, for example through metabolic processes or inflammatory reactions. The reactions of the body are simply too complex.

Using a so-called Langendorff heart -- an isolated rodent heart flushed with a nutrient solution in place of blood -- scientists from the Helmholtz Zentrum Muenchen and the TU Muenchen were for the first time able to show that nanoparticles have a clearly measurable effect on the heart. When exposed to a series of commonly used artificial nanoparticles, the heart reacted to certain types of particles with an increased heart rate, cardiac arrhythmia and modified ECG values that are typical for heart disease.

"We use the heart as a detector," explains Professor Reinhard Nießner, Director of the Institute of Hydrochemistry at the TU Muenchen. "In this way we can test whether specific nanoparticles have an effect on the heart function. Such an option did not exist hitherto."

Scientists can also use this new model heart to shed light on the mechanism by which the nanoparticles influence the heart rate. In order to do this, they enhanced Langendorff's experimental setup to allow the nutrient solution to be fed back into the loop once it has flown through the heart. This allows the scientists to enrich substances released by the heart and understand the heart's reaction to the nanoparticles.

According to Stampfl and Nießner, it is very likely that the neurotransmitter noradrenaline is responsible for the increased heart rate brought on by nanoparticles. Noradrenaline is released by nerve endings in the inner wall of the heart. It increases the heart rate and also plays an important role in the central nervous system -- a tip-off that nanoparticles might also have a damaging effect there.

Stampfl and his team used their heart model to test carbon black and titanium dioxide nanoparticles, as well as spark-generated carbon, which serves as a model for airborne pollutants stemming from diesel combustion.

In addition, silicon dioxide, different Aerosil silicas used e.g. as thickening agents in cosmetics, and polystyrene were tested. Carbon black, spark-generated carbon, titanium dioxide and silicon dioxide led to an increase in the heart rate of up to 15 percent with altered ECG values that did not normalize, even after the nanoparticle exposure was ended. The Aerosil silicas and polystyrene did not show any effect on the heart function.

This new heart model may prove to be particularly useful in medical research. Here, artificial nanoparticles are increasingly being deployed as transportation vehicles. Their intrinsically large surfaces provide ideal docking grounds for active agents. The nanoparticles then transport the active agents to their destination in the human body, e.g. a tumor.

Most of the initial prototypes of such "nano containers" are carbon or silicate based. So far, the effect of these substances on the human body is largely unknown. The new heart model could thus serve as a test organ to help select those particles types that do not affect the heart in a negative way.

Artificial nanoparticles are also used in many industrial products -- some of them since decades. Their small size and their large surfaces (compared to their volume) impart these particles with unique characteristics.

The large surface area of titanium dioxide (TiO2), for example, leads to a large refractive index that makes the substance appear brilliant white. It is thus often used in white coating paints or as a UV blocker in sunscreens. So-called carbon black is also a widely used nanoparticle (mainly in car tires and plastics) with over 8 million tons produced annually. The small size of these nanoparticles (they measure only 14 nanometers across) makes them well suited as dyes, e.g. in printers and copying machines.

With their enhanced Langendorff heart, the researchers have now for the first time developed a measurement setup that can be used to analyze the effects of nanoparticles on a complete, intact organ without being influenced by the reactions of other organs.

The heart is a particularly good test object. "It has its own impulse generator, the sinus node, enabling it to function outside the body for several hours," Andreas Stampfl, first author of the study, explains. "Additionally, changes in the heart function can be clearly recognized using the heart rate and ECG chart."

"We now have a model for a superior organ that can be used to test the influence of artificial nanoparticles," Nießner explains further. "The next thing we want to do is to find out why some nanoparticles influence the heart function, while others do not influence the heart at all."

Both manufacturing process and shape may play an important role. Hence, the scientists plan further studies to examine the surfaces of different types of nanoparticles and their interactions with the cells of the cardiac wall.

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Mechanism of sculpting the plasma membrane of intestinal cells identified

Islamabad, Aug 4 (Newswire): The research group of Professor Pekka Lappalainen at the Institute of Biotechnology, University of Helsinki, has identified a previously unknown mechanism which modifies the structure of plasma membranes in intestinal epithelial cells.

Unlike other proteins with a similar function, the new protein -- named 'Pinkbar' by the researchers -- creates planar membrane sheets. Further research investigates the potential connection of this protein with various intestinal disorders.

A dynamic plasma membrane surrounds all eukaryotic cells. Membrane plasticity is essential for a number of cellular processes; changes in the structure of the plasma membrane enable cell migration, cell division, intake of nutrients and many neurobiological and immunological events.

Earlier research has shown that certain membrane-binding proteins can 'sculpt' the membrane to generate tubular structures with positive or negative curvature, and consequently induce the formation of protrusions or invaginations on the surface of the cell. These membrane-sculpting proteins are involved in various vital cellular processes and can control the shape of the plasma membrane with surprising precision. Many of them have also been linked to severe diseases such as cancer and neurological syndromes.

Identified by Anette Pykäläinen, a member of Professor Lappalainen's group who is currently finalising her dissertation, the new membrane sculpting protein has a different mechanism than other proteins studied previously. Instead of generating positive and negative curvature, the Pinkbar protein is able to produce planar membrane sheets.

Lappalainen's group determined the membrane-sculpting mechanism of Pinkbar in collaboration with an American research group. In humans, Pinkbar is only found in intestinal epithelial cells where it may be involved in the regulation of intestinal permeability.

In the future, it will be important to identify the exact physiological function of Pinkbar in intestinal epithelial cells and to study the possible links of this protein to various intestinal disorders.

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Marine's dream of an Afghan national water polo team advances

Friday, 2 August 2013

San Diego, Aug 3 (Newswire):  For three years, Marine Warrant Officer Jeremy Piasecki has been trying to organize a national water polo team for Afghanistan.

His theory is simple: the people of such a war-torn land need sports heroes too.

When an Afghan won a bronze medal in the tae kwon do competition at the 2008 Olympic Games, cheers erupted not just in the capital, Kabul, but from the mountainous east to the deserts of the west.

But how do you train a water polo team in a land-locked country with few swimming pools and no history of aquatic sports?

Answer: a trip to Southern California, which is to water polo what Texas is to high-school football. The first and most expensive step has been to find a way to get the athletes here.

Now, Piasecki has gotten a pledge from commercial airline employees to provide transportation for 10 athletes, several of them members of the Afghan army. He's working with the State Department to get visas.

Their tentative arrival date is mid-November. The next step for Piasecki is to find enough sponsors to house and feed the athletes.

"If it was easy, I wouldn't be doing it," he said.

Piasecki has been focused on water polo since he played at Corona del Mar High in Newport Beach and Orange Coast College in Costa Mesa. He coached for Temescal Canyon High in Lake Elsinore and the Fallbrook Associated Swim Team.

Enthusiasm notwithstanding, fundraising for what appears a long-shot endeavor has been slow. Adding to the difficulty is the fact that Piasecki is no longer stationed in Afghanistan.

He deployed last year to Stuttgart, Germany. He's saving up his leave time so he can come to Southern California to be with the team during the stay, which he hopes lasts through February.

The war has provided its own brand of setbacks: three of Piasecki's would-be players have been killed in combat. Others have decided it is too dangerous to leave their families while the fighting continues.

"They have endured hardships that most Americans and those in the western world cannot fathom," Piasecki said of his athletes. "They have had their homes destroyed, family members killed, have had to live in exile in other countries....But they still find ways to smile, laugh [and] enjoy camaraderie."

Bahram Hojreh, a former water polo player at UC Irvine and now club director of Los Al Water Polo in Los Alamitos, is arranging training sessions and matches for the Afghans. A large squad of volunteers, Hojreh said, meets weekly.

While others may have gotten discouraged, Hojreh stayed optimistic. "I knew this day would come," he said. "But we will not be satisfied until all details of the trip are covered."

Scott Tanner, head of sport development for the Huntington Beach-based USA Water Polo, which promotes water polo clubs nationwide, said Piasecki is "an inspiration for anyone in the U.S. involved in the sport, an example of overcoming incredible obstacles to put together a team."

Tanner recently hired organizers to spread the sport in Chicago and Orlando, Fla. It's a job perfectly suited for Piasecki, when he leaves the Marine Corps, Tanner said:

"If he ever gets back to the U.S., I want him to work for me. He has the moxie."

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