Booster Shots

Oddities, musings and news from the health world

Category: Rodent

Rodent of the Week: Athletes! You must win at home

July 9, 2010 |  1:00 pm

Rodent_of_the_week There was good reason to be worried when the Lakers lost that second game of the NBA championship playoff series against Boston. The loss was at home. According to new animal research, winning at home appears to be important to the male species' ability to prepare for, and win, future conflicts.

In a study with mice, researchers showed that experiencing a win caused changes in the brains that enhanced the ability to win in the future. Researchers also found that winning at home had a particular effect, causing more activity in male hormone receptors in brain regions thought to influence social aggression.

The researchers paired territorial male mice who had winning experience -- sort of macho male mice that, by the way, are a species of California mice called Peromyscus californicus -- with smaller and sexually inexperienced male mice in various settings, such as home cages and neutral settings. Naturally, the mice fought. The researchers then examined the brains of the mice and compared them to similar mice that were not paired for fights. The mice that won both home and away victories had increased expression of hormone receptors in their brains. But only the brains of mice that won in their home cages showed increased hormone sensitivity in two areas of the brain thought to control motivation and reward. Mice that won at home also won more fights with larger and tougher mice when fighting in neutral locations.

The experience of winning, especially at home, appears to actually change the brains of mice. Perhaps this phenomenon extends to other species. In this somewhat dense conclusion, the authors wrote their results "are therefore provocative because they suggest a mechanism through which environmental context modulates socially induced changes to the functional properties of neural circuits that control behavioral motivation and reinforcement."

The study, released online Tuesday in the Proceedings of the National Academy of Sciences, was conducted by researchers at the University of Wisconsin.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: closing in on a universal flu vaccine

July 2, 2010 |  1:00 pm

Rodent_of_the_week universal influenza vaccine Flu viruses mutate rapidly, meaning that vaccines against the flu have to be continually updated to target the latest strains. Moreover, antiviral medications to combat flu sometimes become ineffective because of viral mutations. Thus, finding a so-called universal flu vaccine that could be used against a wide range of viruses over a longer period of time has been a long-held dream of medical experts and the subject of a lot of research.

Scientists reported this week that they have taken another step toward a possible universal flu vaccine. They discovered a target on the influenza A virus that has not changed much -- unlike other regions of the virus -- called influenza matrix 2 protein (M2e). The researchers then found rare, naturally occurring antibodies in humans that target the protein. When these antibodies were given to mice infected with influenza, 60% to 80% recovered compared to a 10% survival rate in the untreated mice. The antibodies protected against two influenza strains: seasonal human H1N1 and an avian flu, H5N1.

The study was completed by researchers at the University of Wisconsin-Madison, University of Tokyo, Johns Hopkins University and Theraclone Sciences of Seattle. It was published Monday in the Proceedings of the National Academy of Sciences.

While humans can produce these antibodies against the M2 protein as part of the immune system's natural response, levels appear to be too low to trigger enough protection. However therapeutic levels of antibodies might create the necessary protection.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: fixing jet lag and circadian rhythm disorders

June 25, 2010 |  1:06 pm

Rodent When our circadian rhythms are thrown out of whack -- either by jet travel, shift work or sleeplessness -- our bodies object, according to a wealth of emerging research. The risk of breast cancer, stroke and heart disease rise in shift workers, for example. Finding a way to restore circadian rhythms would not only be helpful to travelers fatigued from jet lag, it could lead to a reduction in disease risk.

A new animal study highlights an interesting approach to the problem. Researchers at the Max Planck Institute for Biophysical Chemistry in Germany used mice that were subjected to jet lag and circadian rhythm disruption (by altering the light and dark cycles they were exposed to). The researchers found that the "clock" genes that are important to reestablishing normal circadian rhythms varies among different organs, such as the kidneys, liver, pancreas and adrenal gland. Further, the workings of the adrenal gland appear to coordinate circadian rhythms by gradually adjusting the release of adrenal hormones, called adrenal glucocorticoids.

"...the adrenal gland has a special role," in returning the circadian rhythms back into their proper alignment, the authors wrote.

The findings suggest a possible approach to treating jet lag and circadian rhythm disorders through the use of corticosteroids.

"Our study thus not only substantiated the importance of glucocorticoid rhythms in jet lag adaptation, but also established an informative experimental animal model to explore the treatment of jet lag and its associated symptoms," they wrote.

A medication called metyrapone, used to treat adrenal insufficiency, could be investigated in humans for treating jet lag.

The study "takes us to a new level of understanding of the molecular control of the resetting of the multitude of internal biological clocks disrupted in a mouse model of jet lag," said the author of a commentary accompanying the study.

The study was released this week in The Journal of Clinical Investigation.

 -- Shari Roan

 Photo credit: Advanced Cell Technology, Inc.

Rodent of the Week: Why women are more vulnerable to psychiatric stress

June 18, 2010 |  5:13 pm

It’s well known that women are more susceptible to some kinds of psychiatric disorders than men. For instance, studies have found that depression and post-traumatic stress disorder are twice as common among women as among men. But why?

Rodent One theory involves a brain hormone called corticotropin-releasing factor, or CRF. It is responsible for kicking off the stress response, and it is regulated by the female sex hormone estrogen. So perhaps estrogen causes female and male brains to respond differently to CRF.

To test this, scientists at Children’s Hospital of Philadelphia and the nearby Thomas Jefferson University subjected male and female rats to a swim stress test. Then they studied their brains in minute detail.

It turned out that the female rats were more responsive to CRF – it registered more strongly in their brains than it did in the male rats. What’s more, the female rats weren’t able to tone down the hormone after their stressful swims. But the male rats were – their brain cells changed in a way that prevented some of the CRF from doing its usual job.

“The findings identify molecular and cellular mechanisms that could result in enhanced sensitivity of female rats to CRF and a decreased ability to adapt to excessive CRF,” the researchers wrote. But they cautioned that further research is needed to see if the same gender differences are at play in human brains.

The study was published this week in the June issue of Molecular Psychiatry.

-- Karen Kaplan

Photo: Advanced Cell Technology Inc.

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Rodent of the Week: How habits are formed

June 11, 2010 |  1:00 pm

Rodent_of_the_week When I was in high school, I had to drive a long distance on a freeway to get to school. After arriving, I often wondered how I got there. I didn't remember the drive or even thinking about driving.

This feeling is a common (and, yes, somewhat scary) experience that a group of neuroscientists think they can better explain. In an experiment with rats, researchers at MIT identified two distinct neural circuits in the brain that show distinct changes when the rats were learning to navigate a maze and, later, after they mastered the task.

The rats were placed in a maze that had chocolate sprinkles at the end. The activity in specific parts of their brains was analyzed as they learned the maze, which included a T-juncture where they had to stop and choose to turn right or left. The rats performed the maze repeatedly until they had learned it.

The study showed that one specific neural circuit became stronger with practice. A second neural circuit showed high activity occurring at times when the rats had to make a decision in the maze. But as they learned the maze, activity in this circuit declined. The task had become habitual.

So, arriving at school in one piece wasn't just a matter of luck. "It is good to know that we can train our brains to develop good habits and avoid bad ones," the lead author of the study, Ann Graybiel, said in a news release.

Understanding how specific regions of the brain change through learning could help in developing new treatments for brain-based diseases. The study was published Thursday in the journal Neuron.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: How acupuncture eases pain

June 4, 2010 |  1:00 pm

Rodent Acupuncture seems so mysterious. How can sticking needles into the body cause physical changes, such as pain or nausea relief or an enhanced immune system?

Researchers working on mice say they have a clue. They have identified a molecule, called adenosine, that seems to be involved in generating the physical effects seen in acupuncture. Adenosine is a natural substance known for helping to regulate sleep and for its anti-inflammatory properties. It also acts as a natural painkiller, developing in the body after an injury to stop nerve signals that are screaming "pain!" But scientists at the University of Rochester Medical Center found that the substance is also active in deeper tissues in the body that are affected by acupuncture.

In the experiment, researchers performed acupuncture on mice that had discomfort in one paw. The mice received a 30-minute acupuncture treatment at a point near the knee. The study showed that in mice with normal functioning levels of adenosine, acupuncture reduced pain by about two-thirds. During and after the treatment, the level of adenosine in the tissues near the needles was 24 times greater than before the treatment. But  the treatment had no effect on mice that lacked the adenosine receptor.

The researchers also tested the effects of a cancer drug called deoxycoformycin that makes it harder for the tissue to remove adenosine. Adding this drug significantly boosted the effects of the acupuncture.

"Acupuncture has been a mainstay of medical treatment in certain parts of the world for 4,000 years, but because it has not been understood completely, many people have remained skeptical," the lead author of the study, Maiken Nedergaard, a neuroscientist, said in a news release. "In this work, we provide information about one physical mechanism through which acupuncture reduces pain in the body."

The study was published online this week in the journal Nature Neuroscience.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: A link between the immune system and mental illness

May 28, 2010 |  1:00 pm

Rodent_of_the_week Little is known about the causes of severe mental illnesses. Genes and environmental factors are thought to contribute. But more specific biological processes, still not yet clear, probably contribute to brain dysfunction that results in hallucinations, psychosis and compulsive behavior.

A clue from a study with mice has emerged that links mental illness, particularly obsessive-compulsive disorder, with immune system processes. Mario Capecchi, a distinguished professor of genetics at the University of Utah, found that mutant mice who pull out their hair compulsively (a condition similar to trichotillomania in humans and a model for mental illness in mice) were cured of their abnormal behavior when they received bone marrow transplants. The study was published online Thursday in the journal Cell.

The mice who groom compulsively, thus pulling out their hair, carry a mutant Hoxb8 gene. Capecchi transplanted normal bone marrow from mice into 10 Hoxb8 mutant mice. Four recovered from their abnormal grooming behavior and six improved. It's not clear why the treatment worked. But cells called microglia are derived from bone marrow, and these same cells are found in the brain. It could be that microglia make substances called cytokines that activate or inhibit nerve cells and influence behavior. Or, microglia might play a role in nerve-signal transmissions. Nevertheless, the connection between the two is worth further investigation, Capecchi said. "That's the surprise: Bone marrow can correct a behavioral defect," he said.

The research is preliminary, however, said Capecchi, who shared the 2007 Nobel Prize in physiology/medicine for developing a way to knock out genes in mice in order to analyze gene function. People with mental illness should not try bone marrow transplants as a cure. The compulsive grooming syndrome in mice can't be considered the equivalent of obsessive-compulsive disorder in humans, said Dr. Steven E. Hyman, a professor of neurobiology at Harvard Medical School, in an editorial accompanying the study.

"Analysis of Hoxb8 mutant mice should help to illuminate such matters as the role of different populations of microglia in the brain," Hyman said. "Moreover, these mice could give rise to sorely needed new hypotheses about the mechanisms underlying human disorders characterized by compulsive behaviors."

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Male fat is different from female fat

May 21, 2010 |  1:01 pm

Men often carry extra weight on their stomachs while women tend to accumulate fat on the butt, hips and thighs. A new mouse study suggests why: It seems that female fat tissue and male fat tissue behave very differently.

Researchers at UT Southwestern Medical Center in Dallas examined mouse genes (fat distribution in mice is similar to humans) and found only 138 genes that were common to both male and female fat cells. That means that fat on men is governed by a largely different gene expression profile than fat on women.

After menopause, women's fat distribution often changes and women become more susceptible to belly fat. A woman's risk of heart disease also rises. The discovery of distinct male and female fat genes might yield clues to understanding what happens after menopause, said the lead author of the study, Dr. Deborah Clegg.

The study also showed that male mice consuming a high-fat diet for 12 weeks gained more weight than female mice on the same diet. The male's fat tissue also became more inflamed than the females' fat. But when the female mice had their ovaries removed to induce menopause, their fat began looking much more like male fat.

"However, estrogen replacement therapy in the mice reduced the inflammation and returned their fat distribution to that of mice with their ovaries intact," Clegg said in a news release.

The study raises the possibility that hormones produced by the ovaries determine where fat is deposited in women. Clegg's future research will focus on whether a type of hormone replacement therapy can be developed for postmenopausal women to protect them from belly fat accumulation and heart disease.

The study was published this week in the International Journal of Obesity.

-- Shari Roan

Rodent of the Week: Is this mouse in pain?

May 14, 2010 |  1:00 pm

Rodent Animal research is critical to advancing medical knowledge. But no one wants our furry friends to suffer. A new study published earlier this week shows that mice, like humans, express pain with facial expressions and that a "mouse grimace scale" can help ensure that animals used in laboratory testing do not suffer.

In the study, published online in the journal Nature Methods, McGill University psychology professor Jeffry S. Mogil used five physical features, such as eye closing, nose and cheek bulges and ear and whisker positions, to track the severity of pain. The rodent coding system can be used by scientists to improve the lives of their research subjects. Moreover, a specific pain scale that researchers can follow could lead to better treatments for pain conditions in humans, said Mogil, an expert in using facial features in humans to assess pain.

Rodent models are vital to research on pain, but there have been few methods for measuring spontaneous pain in the animals, the researchers noted. "The ability to reliably and accurately detect pain, in real time, using facial expression might offer a unique and powerful scientific tool in addition to having obvious benefits for veterinary medicine," they wrote.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Reversing age-related memory loss

May 7, 2010 |  1:00 pm

Rodent_of_the_week In a truly exciting area of neuroscience, researchers reported this week that they were able to identify specific changes in the brain that impair age-related memory and learning in elderly mice. These are the kind of gradual memory glitches that humans begin to experience in their late 40s and continue during the aging process. It appears that epigenetic changes -- changes in the way genes function but that do not involve changes in DNA -- cause this type of memory decline. But reversing these changes may yield treatments for cognitive loss.

Researchers in Germany determined that memory decline became impaired in aging mice around 16 months of age. Examining the mice, they found changes in the proteins that control gene expression in their brains. One particular change was found in enzymes called histone acetyltransferases. When the researchers treated the mice with a drug that reinstated the change in the enzymes and in the gene expression, they saw improved memory function in the mice. The study was published Thursday in the journal Science.

"This study presents a major advance in thinking about the role of histone modifications in synaptic plasticity and memory formation," J. David Sweatt, chairman of the University of Alabama at Birmingham department of neurobiology, said in a commentary accompanying the study. Sweatt, in a paper published recently, showed that drugs that affect histone acetyltransferases also benefit mice with Alzheimer's disease.

"These studies will hopefully lead to more effective prevention strategies to improve quality of life in the aged, as well as contribute to a better understanding of memory," Sweatt said in a news release.

-- Shari Roan

Photo: Advanced Cell Technology Inc.


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