Lessons Learned—Or Overlearned: It Makes All the Difference in How the Brain Copes

Lessons Learned—Or Overlearned: It Makes All the Difference in How the Brain Copes

Study may offer a new therapeutic target for counteracting post-traumatic stress disorder and depression by switching coping methods

	BUM OUT OR BOUNCE BACK?:  New study shows that the level of a protein in the brain's reward circuitry indicates whether a person will withdraw or recover quickly from a traumatic event.

The neural activity and physical behavior of mice recovering from several stressful encounters may illustrate alternative ways that mammals respond to traumatic events.

Researchers at the University of Texas (U.T.) Southwestern Medical Center at Dallas noticed that mice used two primary methods to cope with defeat after being repeatedly pummeled by larger, more aggressive foes: Some of the weaker members withdrew, avoiding all types of social interaction for more than a month, whereas others rolled with the punches, so to speak, quickly bouncing back to their normal behavior.

The observation of different coping mechanisms led the team to probe the animals' brains, where they discovered that the level of a certain protein in its reward circuitry determines whether the mice will be traumatized for several weeks or only temporarily down. Researchers found that levels of neurotrophic factor (BDNF) nearly doubled in the brains of vulnerable mice, a finding that could point to a therapeutic target in humans for combating post-traumatic stress disorder and depression.

In an earlier study, the research team, led by U.T. Southwestern psychiatry professor Eric Nestler, found that levels of BDNF—which is implicated in learning because of its role in creating stronger connections between neurons—increase in the nucleus accumbens in response to chronic stress. (The nucleus accumbens is a region in the rear of the forebrain that plays a role in determining whether a stimulus is rewarding or negative.) This rise in BDNF concentration, the scientists say, results from increased activity of neurons in the ventral tegmental area, a midbrain structure that sends signals to the nucleus accumbens via the chemical messenger dopamine.

"Vulnerability is caused by an increase in the frequency of dopamine impulses; a side-effect of that is an increase in the levels of BDNF," says study co-author Vaishnav Krishnan, a graduate student in Nestler's lab. "Resilient mice overcome this change by counteradapting their gene expression [the suite of genes that act on the nucleus accumbens that are either turned on or off] to clamp down the levels of activity in the ventral tegmental area."

Because the mice involved in the study were genetically similar, researchers ruled out a genetic link to the different responses. "These two end points," Krishnan explains, "are really the manifestations of two different types of coping styles."

According to the researchers, as they plunged into despair, mice that experienced the increase in BDNF levels showed symptoms similar to those of human depression: they interacted less with other mice, lost weight and were not interested in sugar or sexual activity, both of which they naturally find rewarding.

"The increase in BDNF may have an adaptive role normally, allowing an animal to learn that a situation is bad and [to] avoid it in the future," Nestler says. "Under conditions of extreme social stress, susceptible animals may be 'overlearning' this principle and generalizing it to other situations."

The U.T. Southwestern team, in an effort to get a clearer parallel between the animal and human condition, conducted autopsies on the brains of depressed and normal individuals. The group suffering from depression had BDNF levels that were as much as 40 percent higher than their counterparts.

"If we can understand how to promote resilience to [chronic] stress," Krishnan says, "we can find new ways of treating depression…. Off the top of my head, a drug that would decrease the amount of BDNF that's released in response to [dopamine] activity would be a good antidepressant." He cautions, however, that such therapy would have to be localized, so that it did not interfere with the protein's role in learning in other brain regions.

Sexy corals keep 'eye' on moon, scientists say

Sexy corals keep 'eye' on moon, scientists say

Birds do it. Bees do it. Even lowly corals do it — but infrequently, forgoing sex for as long as a year.

Then, at night, just after the full moon, under warm tropic breezes, the corals dissolve in an orgy of reproduction, sowing waters with trillions of eggs and sperm that swirl and dance and merge to form new life. The frenzy can leave pink flotsam.

Scientists discovered the mysterious rite of procreation in 1981 and ever since have puzzled over its details. The moon clearly rules the synchronized mass spawning, which happens during different months in different parts of the globe, but usually in the summer. But how do corals monitor the moon's phases and know when to start mingling?

Today, seven scientists from Australia, Israel and the United States report in the journal Science that corals have primitive photoreceptors, if not true eyes. In experiments, they found that the photosensitive chemicals respond to moonlight as admirably as, well, human lovers.

"This looks to be the smoking gun," Ove Hoegh-Guldberg, a team member at the University of Queensland, said in an interview. "It triggers the largest spawning event on the planet."

Margaret Miller, a coral specialist at the National Oceanic and Atmospheric Administration, called the finding by the group of scientists "a big step forward. It's always been a mystery as to how these animals manage to synchronize themselves."

In recent years, the undersea love-fests have become tourist attractions for divers in the Caribbean, in Australia on the Great Barrier Reef, and other coral havens. Al Giddings, a famous ocean photographer, made a PBS documentary that showed reefs around the Pacific islands of Palau exploding in blizzards of rising sperm and eggs.

Though the scientists involved say more work is needed to determine how the photoreceptor works, the finding is significant because it addresses the spawning's main riddle, marine biologists say. "When I talk about thousands of reefs in the Caribbean releasing their spawn within minutes of each other during a specific phase of the moon, people marvel and ask, 'How do they do it?'" said Alina Szmant, a coral expert at the University of North Carolina, Wilmington. "My answer is always, 'It's a mystery.'"

Now, she said, the discovery provides clues to the puzzle and opens up "a new direction to explore." Biologists say the finding sheds light on hidden aspects not only of coral reproduction but of evolution, suggesting that light receptors arose surprisingly early in the development of animals. Corals emerged more than 500 million years ago, near the dawn of complex life. "Our discovery," the scientists write in Science, suggests that the basic mechanisms for responding to light "were in place at the origins of multicellularity in animals."

People have known about the moon's romantic possibilities for a long time. Shakespeare in "A Midsummer Night's Dream" relies on moonlight to set the mood. The 1987 movie "Moonstruck" features a love story centered on "La Bella Luna."

Corals are actually colonies of individual organisms called polyps, which create the skeletal structure that binds them together. For centuries, scientists held that corals were primitive creatures with no brain or eyes that knew nothing of moonlight or other environmental nuances and reproduced mainly by brooding offspring and bringing forth live young.

In 1981, that dogma began to collapse when graduate students at James Cook University in Australia followed a trail of clues to a nighttime mass spawn on the Great Barrier Reef. Their discovery made the cover of Science in 1984, and a chapter of the 1998 book "The Enchanted Braid" (John Wiley), which called the startling find "a coup for a group of graduate students."

Investigation showed that the swirling eggs and sperm would merge and float away, forming embryonic corals that would sink to the ocean floor and, if conditions were right, found new colonies. Scientists speculated that the moon's phase was important in the ritual because it controlled the tides. But in some places the tides were low and in others high, and scientists now say the moon may simply act as a clock to choreograph sex among more than 100 species of corals.

The photoreceptor discovery is the brainchild of Oren Levy, a young Israeli scientist who traveled to Australia in 2004 to study in Hoegh-Guldberg's laboratory at the University of Queensland. Levy was fascinated by a class of photoreceptors known as cryptochromes. Originally found in plants, they had been tracked to insects and mammals, too. Levy wondered if corals might possess them.

In an interview, he said one clue was that cryptochromes responded to blue light. That frequency can easily penetrate seawater, so much so that reef areas are sometimes known as "blue deserts." Levy and his colleagues studied Acropora millepora, a coral that can grow a foot across or wider and contain thousands of the individual polyps. They found two kinds of cryptochrome arrayed on the coral's outer edges, one of which responded to the light and dark phases of the moon.

"This is the start of the story, not the end," Levy said in an interview. "It will take five more years at least" to uncover the light sensor's full story. The paper's other authors work at Stanford University, Tel Aviv University, the Australian National University and James Cook University.

Peter Vize, a coral specialist at the University of Calgary, called the team's work "big in implications." The discovery, he added, "is opening up a whole pile of questions."

 
A star coral releasing egg and sperm bundles, responding to the moon with
photoreceptors.

Monster Black Hole Busts Theory

Monster Black Hole Busts Theory

A stellar black hole much more massive than theory predicts is possible has astronomers puzzled.

Stellar black holes form when stars with masses around 20 times that of the sun collapse under the weight of their own gravity at the ends of their lives. Most stellar black holes weigh in at around 10 solar masses when the smoke blows away, and computer models of star evolution have difficulty producing black holes more massive than this.

The newly weighed black hole is 16 solar masses. It orbits a companion star in the spiral galaxy Messier 33, located 2.7 million light-years from Earth. Together they make up the system known as M33 X-7.

"We're having trouble using standard theories to explain this system because it is so massive," study team member Jerome Orosz of the University of California, San Diego, told SPACE.com.

The black hole in M33 X-7 is also the most distant stellar black hole ever observed. The findings, detailed in the Oct. 17 issue of the journal Nature, could help improve formation models of "binary" systems containing a black hole and a star. It could also help explain one of the brightest star explosions ever observed.

Black hole eclipse

Black holes can't be seen, because all matter and light that enters them is trapped. So black holes are detected by noting their gravitational effects on nearby stars or on material that swirls around them.

The companion star of M33 X-7 passes directly in front of the black hole as seen from Earth once every three days, completely eclipsing its X-ray emissions. It is the only known binary system in which this occurs, and it was this unusual arrangement that allowed astronomers to calculate the pair's masses very precisely.

The tight orbits of the black hole and star suggests the system underwent a violent stage of star evolution called the common-envelope phase, in which a dying star swells so much it sucks the companion inside its gas envelope.

This results in either a merger between the two stars or the formation of a tight binary in which one star is stripped of its outer layers. The team thinks the latter scenario happened in the case of M33 X-7, and that the stripped star explodes as a supernova before imploding to form a black hole.

However, something unusual must have happened to M33 X-7 during this phase to create such a massive black hole. "The black hole must have lost a large amount of mass for the two objects to be so close," Tomasz Bulik, an astronomer at the University of Warsaw in Poland, writes in related Nature article. "But on the other hand, it must have retained enough mass to form such a heavy black hole."

The team estimates the black hole's progenitor must have shed gas at a rate about 10 times less than models predicted before it exploded.

"[M33 X-7] might thus provide both the upper and lower limits on the amount of mass loss and orbital tightening that can occur in the common envelope," added Bulik, who was not involved in the study.

Twin black holes

If other massive stars also lose very little material during their last stages, it could explain the incredibly luminosity of 2006gy, one of the brightest supernovas ever observed, the researchers say.

One day, the lone star in M33 X-7 will also disappear, notes study team member Jeffrey McClintock of the Harvard-Smithsonian Center for Astrophysics in Cambridge, Mass. "This is a huge star that is partnered with a huge black hole," McClintock said. "Eventually, the companion will also go supernova and then we'll have a pair of black holes."

While 16 solar masses is hefty for a stellar black hole, it is miniscule compared with the black holes thought to lie in the heart of many large galaxies. Such "supermassive" black holes have masses millions to billions times that of our sun, but they are thought to form by mechanisms different from the stellar variety.

This Harvard-Smithsonian Center for Astrophysics handout image received in June 2006 shows the Messier 33...

Pollution-Busting Plants

Pollution-Busting Plants

Transgenic trees and plants may break down the pollutants left behind at sites ranging from former factories to firing ranges

	TRANSGENIC TREES:  Such cuttings of a genetically modified aspen hybrid proved capable of removing benzene, a human carcinogen, from air (pictured here) or trichloroethylene, the most common contaminant at U.S. toxic waste sites, from water.

A French hybrid of an aspen tree may one day rid water supplies of the industrial degreaser—and human carcinogen—trichloroethylene (TCE), one of the most common contaminants at toxic waste sites in the U.S. And the tiny, but tractable, Arabidopsis plant may mop up the residue of RDX, a military explosive blasted into the soils at firing ranges.

"Plants are a good method for remediating soil and water," says Stuart Strand, an environmental engineer at the University of Washington who has worked on creating the genetically modified pollution-gobbling aspen tree. Even in their natural state, such trees and plants absorb environmental contaminants and break them down into harmless components—all with the power of the sun.

To boost this natural process, researchers introduced a cytochrome known as P450 2E1, an enzyme that ordinarily breaks down many contaminants in the livers of humans and other mammals, allowing them to be harmlessly excreted in urine. The problem is that this breakdown can precipitate the formation of so-called free radicals or ionized molecules, which can cause damage in the liver and elsewhere that may lead to cancer. "We figured we would put [P450 2E1] into plants and let it happen outside our bodies," Strand says. 

The researchers used a bacteria to insert the genetic code for this cytochrome isolated from rabbits into the genetic instructions of the hybrid aspen tree, which belongs to the poplar family. When the resulting cuttings, placed in vials, were dosed with TCE, they sucked the contaminant out of the water 53 times faster than unaltered aspens—and removed between 51 and 91 percent of it by the time they were done drinking the poison. "The best of our transgenic poplars lines degrade TCE 121 times better than the average control plants," says University of Washington biochemist Sharon Doty, who led the research, which was published online in Proceedings of the National Academy of Sciences.

Because the cytochrome P450 2E1 works on a variety of contaminants, it also boosted the tree's ability to absorb the chloroform left over after cleaning drinking water, the industrial solvent carbon tetrachloride and even vinyl chloride—although the latter blackened the leaves of the young aspen cuttings. And the benefit was not limited to water. "When we tested if they could remove some of these volatile chemicals directly from air,'' Doty says, "we discovered that they could remove benzene, a known human carcinogen, 10 times faster than control plants."

European and Canadian biologists working with the Arabidopsis plant, a flowering weed, successfully demonstrated that inserting a variant of cytochrome P450 isolated from battlefield bacteria allowed it to break down the RDX left behind in the soil of firing ranges. Such altered Arabidopsis, when drinking RDX-laced water, removed 90 to 97 percent of it, the researchers write in Proceedings of the National Academy of Sciences.

Such tiny weeds, however, do not have the root structure to reach deeper contaminated groundwater, as aspens do. Studies of actual trees in the field will follow as well as how the trees might affect wildlife, such as insects, Strand says.

The ultimate goal, he adds, is to create trees that provide a low-cost option for cleaning contaminated groundwater and sites that might not otherwise be purified due to the expense of chemical and microbial treatments. And, because this aspen only flowers after seven years—and can regrow when cut to the root—such altered trees could be confined to areas where they are needed to consume contaminants over decades. "This ability to prevent flowering is good because we don't want to release the transgene into the environment," Strand says. "By using our trees, you could clean up a site at less cost than any other method. Otherwise, you might not want to clean it up at all."

Drug-Resistant Staph a Widespread Threat

Drug-Resistant Staph a Widespread Threat

(HealthDay News) -- Potentially deadly, drug-resistant staph infections are more common, both in and out of hospitals, than experts once thought, a new study warns.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are the top cause of skin and soft tissue infections among people in hospitals and can result in severe and even fatal disease. In fact, MRSA infections account for almost 19,000 deaths and more than 94,000 life-threatening illnesses each year in the United States.

"Invasive MRSA is an important public health problem," said lead researcher Dr. R. Monina Klevens, an epidemiologist at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta. "We need to do a better job in preventing MRSA infections," she added.

In the study, Klevens' group used data from the Active Bacterial Core surveillance/Emerging Infections Program Network from July 2004 through December 2005 to estimate the incidence of MRSA infection in the United States.

The report is published in the Oct. 17 issue of the Journal of the American Medical Association.

The researchers uncovered 8,987 cases of invasive MRSA. Most of these (58.4 percent) were found in community health care settings, 26.6 percent were in hospitals, 13.7 percent were infections not associated with health care facilities and 1.3 percent could not be classified.

Klevens' team estimated the rate of invasive MRSA in 2005 at 31.8 per 100,000 persons, but that rate was higher for certain populations.

By age, rates of infection were highest for those 65 and older (almost 128 cases per 100,000). Blacks were much more likely than whites to become infected, at 66.5 cases per 100,000 versus about 28 per 100,000, respectively. Men had more cases (37.5 per 100,000) than women (26.3 per 100,000). The lowest rate was for children 5 to 17 years of age, at 1.4 cases per 100,000.

Based on these data, the researchers estimated that there were 94,360 cases of invasive MRSA in the United States in 2005, and 18,650 deaths caused by these infections.

Klevens believes more effort is needed, especially among health care providers, to reduce the number of infections. "This is really a call for action to health care settings that we need to do a better job at preventing MRSA," she said.

One expert agreed that the new study should serve as a warning.

"This is really the first study to quantify how much MRSA is occurring in the United States," said Dr. Elizabeth A. Bancroft, an epidemiologist at the Los Angeles County Department of Public Health and author of an accompanying journal editorial. "The rate of infection is a lot higher than what was expected," she added.

The rate of MRSA is higher than the rate of the four other invasive bacterial diseases that public health officials typically study, Bancroft said. In fact, more people died in 2005 from MRSA infections in the United States than died from AIDS, she noted.

"The MRSA rate is only the tip of the iceberg, because this study only included cases that are invasive," she said. "MRSA, especially in the community setting, is more likely to cause skin infections," she said.

Prevention is relatively simple: People can protect themselves from MRSA by washing their hands, keeping wounds covered and maintaining good hygiene, Bancroft said. "You don't always need antibiotics to treat this infection," she said. "A lot of times, it can be treated by having a doctor drain the pus out."

"The most common way MRSA is spread is from person-to-person," Bancroft said.

In the hospital or other health care facilities, patients should make sure that doctors and nurses wash their hands before touching them, starting an IV or inserting a catheter or other invasive device, Bancroft said.

MRSA in the outside community is most often passed from one person to another through casual contact, such as body contact during sports, sharing towels or athletic equipment, particularly in schools and prisons, Bancroft said.

Outbreaks of staph skin infections are being reported this year in schools across America, and some of them are caused by MRSA, the Associated Press reported on Saturday. Most infections are being spread in school gyms and locker rooms as athletes with minor cuts and abrasions share equipment, experts said.

"Most of these are mild infections," Nicole Coffin, spokeswoman at the U.S. Centers for Disease Control and Prevention, told the AP. "They can be as simple as a pimple or a boil, or as serious as a blood infection."

In a Newport News, Va., high school, four students were infected with staph, one of them carrying the MRSA strain. That patient, a football player, was briefly hospitalized this week, the AP said.

Other outbreaks of a similar nature have occurred in schools in Illinois, Maryland, New York, Ohio, Pennsylvania, and South Carolina, the AP added.