Tag Archives: mice

Study on mice: Exercising later in life can keep your muscles young

Exercising can not only make you feel younger, but it can also actually keep you younger as well. A study on mice suggests that exercising, even later in life, can do wonders for your muscles. In addition to underscoring the importance of staying active, the study could also help us uncover some of the secrets of rejuvenation.

Even though some diseases are inherited, we can still improve our overall health through lifestyle choices such as diet and exercise. Still, whatever the reason, the genes related to some of these conditions must be expressed for them to develop. So how does this happen?

A new study has brought us closer to an answer by mapping the genetic changes involved in rejuvenating the muscle cells of elderly mice put on an exercise program.

Turning genes on and off

The analysis centers on DNA, the “blueprint” for our bodies. DNA consists of four bases, called cytosine, guanine, adenine, and thymine, and the process used to help manage these massive helixes: a methyl molecule composed of one carbon and three hydrogen atoms. These atoms attach themselves to one of the four bases (cytosine) to form what’s known as a CpG site.

When this occurs, the CpG becomes methylated and the site produces proteins to regulate something in the body — whatever that something may be. In contrast, the region becomes unmethylated when you lose that methyl group, turning that gene off. In this way, a process called DNA methylation can promote or inhibit the expression of specific genes — whether it’s stopping a tumor, preventing cancer, or activating genes responsible for causing wrinkles in old age. This process is constant, occurring billions of times a second in every cell throughout the body, and we’re just starting to understand it.

DNA methylation is one of the many mechanisms of epigenetics, where inborn or acquired changes in DNA don’t touch the actual sequence – meaning a person can potentially reverse things like fat deposits through diet or exercise. More and more studies are starting to suggest that this is an unharnessed and robust process, linked to longevity and the regulation of lifespan in most organisms on earth.

The current study attempts to further this theory using lifestyle interventions such as exercise to roll back genetic aging in skeletal muscle – measuring the animal’s ‘epigenetic clock’ for accuracy. This clock is measured via methylation levels in the blood to reflect exposures and disease risks independent of chronological age, providing an early-warning system and a true representation of a period of existence.

Kevin Murach, an assistant professor at the University of Arkansas, says, “DNA methylation changes in a lifespan tend to happen in a somewhat systematic fashion. To the point, you can look at someone’s DNA from a given tissue sample and with a fair degree of accuracy predict their chronological age.”

Using exercise to turn back the clock

The study design was relatively simple: mice nearing the end of their natural lifespan, at 22 months, were given access to a weighted exercise wheel to ensure they built muscle. They required no coercion to run on the wheel, with older mice running from six to eight kilometers a day, mostly in spurts, and younger mice running up to 10-12 kilometers.

Results from the elderly mice after two months of weighted wheel running suggested they were the epigenetic age of mice eight weeks younger, compared to sedentary mice of the same maturity.

The team also used the epigenetic clock to map a multitude of genes involved in the formation and function of muscles, including those affected by exercise. Blood work indicated that the genes usually over methylated (hypermethylated) in old age resumed normal methylation in the active aged mice, unlike those mapped in their sedentary counterparts.

For instance, the rbm10 gene is usually hypermethylated in old age, disrupting the production of proteins involved in motor neuron survival, muscle weight & function, and the growth of striated muscle. Here it was shown to undergo less methylation in older mice who exercised, improving its performance. Normal methylation levels also resumed across the Timm8a1 gene, keeping mitochondrial function and oxidant defense at workable levels – even where neighboring sites exhibited dysfunctional epigenetic alterations.

More work is needed to harness DNA methylation

Murach notes that when a lifespan is measured incrementally in months, as with this mouse strain, an extra eight weeks — roughly 10 percent of that lifespan — is a noteworthy gain, further commending the importance of exercise in later life.

He adds: that although the connection between methylation and aging is clear, methylation and muscle function are less clear. Despite these sturdy results, Murach will not categorically state that the reversal of methylation with exercise is causative for improved muscle health. “That’s not what the study was set up to do,” he explained. However, he intends to pursue future studies to determine if “changes in methylation result in altered muscle function.”

And, “If so, what are the consequences of this?” he continued. “Do changes on these very specific methylation sites have an actual phenotype that emerges from that? Is it what’s causing aging or is it just associated with it? Is it just something that happens in concert with a variety of other things that are happening during the aging process? So that’s what we don’t know.”

He summarizes that once the medical community has mapped the mechanics of dynamic DNA methylation in muscle, their work could provide modifiable epigenetic markers to improve muscle health in the elderly. 

These adorable mice can regenerate their kidneys without scarring

This tiny mouse has Wolverine-like regeneration abilities. Image credits: Marcel Burkhard.

Spiny mice are a group of rodents with scaled tails. Their coats have stiff guard hairs similar to the spines of a hedgehog — hence the name “spiny” mice.

These mice are well-known for their ability to heal severe skin wounds without even a scar. In a new study, researchers wanted to see if their regeneration abilities also extend to other organs.

No scars allowed

It wasn’t easy to set the study up. Researchers had to establish a spiny mouse colony at Seattle Children’s Research Institute, says Mark W. Majesky of the Seattle Children’s Research Institute from the University of Washington. But thanks to initial funding from the W. M. Keck Foundation, researchers were able to get going.

They exposed spiny mice to conditions that cause serious kidney injuries in other types of mice (non-spiny ones). The researchers found that although initially, spiny mice suffer damage just like their counterparts, they were able to completely regenerate — furthermore, they showed no signs of fibrosis (or scarring).

“We used experimental kidney injuries that are known to produce extensive renal fibrosis leading to complete kidney failure in laboratory mice. Using the same kidney injury models, we found that spiny mice naturally repair the injury-induced damage to the kidney and fully regenerate kidney function with no signs of renal fibrosis,” Majesky told ZME Science.

This is the first time this type of regenerative ability has been demonstrated in a mammal and it could have big implications for human research.

Researchers compared the genes that spiny mice express in the healing process, compared to the genes of “regular” mice, which don’t have the ability to regenerate. They found differences in 843 genes in six clusters — it’s likely here that the ‘magic’ is happening.

The study also found a delayed response by macrophages — specialized cells involved in the detection and destruction of pathogens. These macrophages are known to play a role in fibrosis, so essentially, the mice are delaying an immune response to avoid scarring.

“When we looked closer at gene expression in these experiments, we found that the spiny mouse genome appears to be poised to initiate a regenerative wound healing response at the time of organ injury. By contrast, laboratory mice initiate a proinflammatory response leading to interstitial cell activation, extensive organ fibrosis, and loss of organ function,” the researcher added.

Tackling renal problems in humans

Millions of people on the globe are affected by kidney issues. In the US alone, there are 600,000 patients with kidney failure and over 450,000 patients (including children) currently on dialysis, says Majesky. Most of those patients have progressive kidney fibrosis leading to kidney failure.

“We conducted our research with those individuals in mind. Since there are very few effective therapies for progressive renal fibrosis, our objective was to look to nature for a different way to approach the problem of fibrosis-driven kidney failure,” Majesky told ZME Science.

“The global health burden for loss of vital organ function due to progressive tissue fibrosis is enormous,” says Mark Majesky, a principal investigator at Seattle Children’s Research Institute and professor of pediatrics at the University of Washington. “Very few treatment options are currently available for patients with end-stage kidney disease or similar degenerative fibrotic diseases of the heart, lungs, liver, or reproductive organs. Our group took a different approach to this problem and looked to nature to provide clues that might lead to novel therapies.”

When they learned about the ability of spiny mice to regenerate skin damage without scarring, Majesky and colleagues immediately wanted to see if that ability extends to other organs.

“Our initial experiments were designed to test the possibility that scarless wound healing might extend to
internal vital organs, such as the kidney,” Majesky notes.

If researchers can zoom in on the mechanisms through which the mice achieve this regeneration, perhaps they can also replicate it on humans. While that’s still a ways off, for now, it’s still an avenue well worth investigating.

“We have opened a new window on the development of possible therapies for chronic kidney disease, that may perhaps apply to other organs that similarly exhibit loss of function due to progressive tissue fibrosis,” Majesky says.

“Our goal is to learn what nature has done in evolving a mammalian genome that heals tissue injury by regeneration without fibrotic scarring and apply the lessons learned to the development of new therapies for kidney disease,” adds Daryl M. Okamura, also of Seattle Children’s Research Institute, and co-author of the study.

Researchers are also hopeful that, with work also progressing in related fields of medicine, the findings could be soon applied in human treatment.

“Given that other investigators in many different fields are developing small molecule drugs to target key regulators of the mammalian epigenome, it may be that in the not too distant future we will be able to apply the lessons learned from nature and the remarkable spiny mouse to human kidney disease,” Majesky concludes.

Journal Reference: iScience, Okamura et al.: “Spiny mice activate unique transcriptional programs after severe kidney injury regenerating organ function without fibrosis” https://www.cell.com/iscience/fulltext/S2589-0042(21)01238-4 

Mice can develop neural signs of depression when forced to watch other mice experiencing stress

Depression is a global problem, affecting an ever-growing number of individuals. In a bid to better understand its physiological underpinnings, a team from the Tokyo University of Science has explored how neural deterioration in areas of the brain such as the hippocampus, as well as physical and psychological stress, is tied to depression.

Image credits Tibor Janosi Mozes.

There are several theories regarding why and how depression emerges, both from psychological and physiological factors. In regards to the latter, the “neurogenic hypothesis of depression” has garnered a lot of scientific interest. It states that depression can stem from physical degradation in areas of the brain such as the hippocampus, degradation which can be incurred by stress.

While the link between physical stress and depression has been investigated in the past, much less is known about the effects of psychological stress. A new study aims to give us a better understanding of this topic, using mice as a model organism.

A grinding toll

“The number of individuals suffering from depression has been on the rise the world over. However, the detailed pathophysiology of depression still remains to be elucidated. So, we decided to focus on the possible mechanism of psychological stress in adult hippocampal neurogenesis, to understand its role in depressive disorders,” says Prof. Akiyoshi Saitoh from Tokyo University of Science, co-lead author of the study.

“We have found out that chronic mental stress affects the neurogenesis of the hippocampal dentate gyrus. Also, we believe that this animal model will play an important role in elucidating the pathophysiology of depression, and in the development of corresponding novel drug.”

For the study, the team exposed mice to “repeated psychological stress” in order to test how this impacts hippocampus degeneration in their brains. The experiment consisted of making the mice experience chronic social defeat stress (cSDS) via their peers — a source of psychological stress for the animals, as they are a highly social species. Chronic social defeat stress is an experimental tool through which stress is induced in a subject (such as a mouse), the ‘naive mouse’ to ‘aggressor’ mice. As part of this research, the mice were made to witness the naive mice, who were participating in the stressful situation.

After this exposure, the team analyzed their brains to measure the level of degradation it produced in key brain areas, as well as noting changes in behavior.

First off, they report that the mice exposed to this repeated source of stress started exhibiting behavioral issues such as social withdrawal, indicative of depression. In their brains, more specifically the dentate gyrus area of the hippocampus, the team recorded a decreased survival rate of new-born neurons compared to those of controls. This area is heavily involved in memory and sensory perception.

Lower new-born neuron survival rates persisted for up to four weeks after the animals were exposed to the stress-inducing scenarios. Chronic treatment with antidepressant fluoxetine was efficient in restoring neuronal survival rates for these mice. Other characteristics, such as cell growth, differentiation, and maturation rates were not impacted by stress in the experimental mice (as compared to controls), the team adds.

The authors link neural degradation in the hippocampus to the emergence of depression through the fact that avoidance behaviors in the experimental mice was “significantly enhanced” 4 weeks after the last stress-inducing exercise, compared to the first day after it. This behavior, they explain, is likely produced by degradation mounting in neurons of the hippocampus following the experience.

Although these findings have not yet been validated in humans, the authors believe that they can form an important part of understanding how depression emerges in the brain even among us. Further work is needed to validate the results and see whether they translate well to humans, however.

The paper “Chronic vicarious social defeat stress attenuates new-born neuronal cell survival in mouse hippocampus” has been published in the journal Behavioural Brain Research.

Give lab mice a better life and the science will also get better

The long-term emotional wellbeing of mice can affect their behavior — and that’s important for researchers using them for models.

To say that lab mice are important to science is a hell of an understatement. Mice have been used in biomedical research for centuries. Entire fields of research wouldn’t even exist without animal models. The humble mouse has proven valuable in everything from genetics to psychology.

But, in recent years, researchers have become more and more aware that there is a problem with lab mice; or rather, several. For instance, there’s almost no diversity in lab mice, which means that the vast majority of studies are carried out on male mice. This has cascading effects on multiple levels, and to put it simply, it means that mouse studies might not be all that representative for women.

Here’s another issue that researchers should no longer ignore: mice’s feelings.

Animals experience a broad range of emotions that are crucial for their decisions, behavior, and biology. For the most part, however, science has largely been uninterested in the positive emotions lab mice can exhibit. That’s a problem, a team of British researchers is saying. If we’d focus a bit more on making them happy, we’d be getting better results in lab tests, according to a new study.

“Our results also demonstrate that repeated negative events can have a cumulative effect to reduce resilience in laboratory animals, which has significant implications for animal welfare,” the authors write.

To test how mice react to negative emotions, researchers… well… gave rats negative emotions. They lifted the mice by the tail when it was time to handle them, a process known to annoy and startle mice. This tail-lifted group was compared with another group that was handled via the less stressful “tunnel handling” technique, where mice hang out in a plastic tube instead of being physically grasped.

When it came to positive stimuli (like being given some sugar water), the two groups responded the same. But when it came to negative stimuli, there were big differences between the two groups.

Lead researcher, Dr. Jasmine Clarkson notes:

“Animals have emotions that are affected by what happens to them in their everyday lives. Like us, they can get anxious and depressed, but how does that change their experiences of the good and the bad things in life? We found that anxious and depressed laboratory mice are more disappointed when something bad happens, but their low mood has no effect on how elated they are when something good happens.”

“So if we apply that to the welfare of our lab animals, it means poor welfare still allows animals to appreciate reward but it makes them less resilient and potentially reduces the reliability of biomedical experiments. These are important findings which emphasize the benefits of the highest level of care that we should adhere to.”

For starters, this suggests that the tunnel handling method should be used more widely, ensuring that handling is the least stressful treatment possible.

But more importantly, it suggests that lab animal welfare and good science go hand in hand — and it’s not a trivial matter. Psychology and medicine are plagued by a replication crisis, and it’s plausible that a part of that problem comes from animal model studies. Researchers are struggling to recreate each other’s findings for reasons that are not clear. For instance, if someone carried out a study handling mice directly, and someone else tried to replicate it using a tunnel, they might get different results.

If something as simple as handling can help address this issue, then it’s definitely something worth addressing; and if it makes the lives of lab mice a bit more pleasant, what’s not to like?

The study was published in Proceedings of the Royal Society B.

Nose-administered COVID-19 vaccine shows promise in mice

New research at the Washington University School of Medicine (WU) in St. Louis is closing in on an effective vaccine against the coronavirus.

Image via Pixabay.

The researchers have developed a single-dose vaccine that’s deliverable via the nose and effective at preventing infection with SARS-CoV-2 in mice. The results warrant further research on primates and, eventually, humans, the team writes. If these tests are successful, this would be the only COVID-19 vaccine deliverable via the nose, not an injection.

A nose for vaccines

“We were happily surprised to see a strong immune response in the cells of the inner lining of the nose and upper airway—and a profound protection from infection with this virus,” said senior author Michael S. Diamond, MD, Ph.D.

“These mice were well protected from disease. And in some of the mice, we saw evidence of sterilizing immunity, where there is no sign of infection whatsoever after the mouse is challenged with the virus.”

The team says that the vaccine had a particularly strong effect in the nose and deeper respiratory tract of the mice. Since this area is where the virus first establishes its foothold, fighting it off here can prevent an infection altogether.

The vaccine was created by inserting the coronavirus’ distinct spike protein, the biochemical structure it uses to enter our cells, into another type of virus — an adenovirus, the class that causes the common cold. This adenovirus forms the base of the vaccine. It was further manipulated by the researchers to make it unable to cause any illness and then introduced into the nose. This way, our cells can interact with it and ‘see’ the spike protein, which enables our body to create an appropriate antibody, while being completely safe.

The team adds that they added two mutations to the spike protein to keep it stable in a specific shape, making it easier for our bodies to generate antibodies.

Still, the biggest news regarding this vaccine is the method of administration. Adenoviruses are often used as mediators in vaccines, for example in those for Ebola and tuberculosis, but they’re administered through injection. What few other vaccines we currently have that are administered via the nose use a weakened, live virus. This limits the cases where they can be administered, and also are likely to pose a greater risk, as the viruses can, at least in theory, replicate inside the host.

“The nose is a novel route, so our results are surprising and promising. It’s also important that a single dose produced such a robust immune response,” says co-senior author David T. Curiel, MD, Ph.D., the Distinguished Professor of Radiation Oncology at WU.

“Vaccines that require two doses for full protection are less effective because some people, for various reasons, never receive the second dose.”

So did it work? The team says yes. They compared the intranasal administration technique to that of an intramuscular injection. The injected one caused the mice to become resistant to pneumonia, but didn’t prevent a SARS-CoV-2 infection in the respiratory tract. In a human equivalent, this would make patients experience a less-severe form of COVID-19, but wouldn’t protect them against becoming infected or spreading the virus.

The intranasal vaccine, meanwhile, completely prevented infection in the upper and lower respiratory tract. In a human equivalent, this would completely prevent an infection from taking root, and would stop carriers from spreading the disease.

Naturally, we should temper our enthusiasm — the vaccine has only been tested on mice so far. Until more research can be done, especially using human participants, this vaccine is far from being confirmed as efficient.

The paper “A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2” has been published in the journal Cell.

Mice have different facial expression depending on how they feel — a doorway to the origin of emotions

The facial expressions of mice reflect their internal emotional state, similarly to humans. The findings offer a possible neural mechanism of emotions. Credit: MPI of Neurobiology / Kuhl.

There are over 7,000 languages spoken in the world today. And while there is a lot of common ground in how people express body language in different cultures, one thing seems to be ubiquitous to humans: facial expressions as reactions to prime emotions, such as fear, joy, or disgust.

According to new research, mice also have facial expressions that they cannot readily control and which appear predictably under certain stimuli. This important work might help unravel the evolutionary origin of emotions.

The universality of emotional facial expressions

Charles Darwin was the first to suggest that the facial expressions of emotions are universal. In fact, this was one of the centerpieces of his theory of natural selection, proposing that emotions and their expressions were biologically innate and evolutionarily adaptive, and that similarities in them could be seen phylogenetically.

This particular idea was not validated until the 1970s, when studies showed high cross-cultural agreement in judgments of emotions in faces by people in both literate and preliterate cultures.

Over 100 modern studies published since then — which have been carried out by different researchers from different institutions using different methodologies with participants from different cultures — have converged towards the same set of results, pointing towards the universal facial expressions of at least seven emotions: anger, contempt, disgust, fear, joy, sadness, and surprise.

Of mice and facial expressions

In a new study, researchers at Max Planck Institute of Neurobiology in Germany used machine vision to study the facial expressions of mice in relation to the emotions that they experienced.

Their work showed that the facial expressions of mice were not just a reaction to the environment, but rather a reflection of their internal emotional state. The researchers were able to reliably link five emotional states to the facial expressions of mice: pleasure, disgust, nausea, pain, and fear, all of which were clearly distinguishable for the computer algorithms. 

“Mice that licked a sugar solution when they were thirsty showed a much more joyful facial expression than satiated mice,” explains Nadine Gogolla, who led the study. 

When they were offered a slightly salty solution to quench their thirst, the mice exhibited a “satisfied” facial expression, while a very salty solution produced a “disgusted” face as a response.

The researchers also scanned the brains of the mice in order to investigate how neural activity in different brain regions drives facial expressions.

When they activated certain neurons with light shined on specific brain areas known to play a role in emotional processing, the mice exhibited predictable facial expressions.

One such brain area is the insular cortex, where the emotionally-related behavior and perception of emotions are processed in both humans and animals. Neurons in the insular cortex reacted with the same strength and at exactly the same time as the mouse changed facial expression.

This is actually tremendously important research. Emotions are an incredibly important aspect of human life, but research so far has not been able to precisely identify the mechanisms responsible for all the complex feelings that we have.

“We humans may notice a subtle facial change in the mice, but we can only recognize the emotion behind it with a great deal of experience and can hardly ever determine its intensity,” says Nejc Dolensek, the study’s lead author. “With our automated face recognition system, we can now measure the intensity and nature of an emotion on a timescale of milliseconds and compare it to the neuronal activity in relevant brain areas.” 

All of these results suggest that there may be “emotion neurons”, which are dedicated to processing and expressing emotion in the body, with each sensation being controlled by a different type of neuron.

“By recording facial expressions, we can now investigate the fundamental neuronal mechanisms behind emotions in the mouse animal model,” explains Nadine Gogolla. “This is an important prerequisite for the investigation of emotions and possible disorders in their processing, such as in anxiety disorders or depression.”

The findings appeared in the journal Science.

Scientists create supermice that can see infrared light

Could science ever grant us superhuman abilities? A new study suggests that this, indeed, possible after researchers used a nanoparticle solution to grant ordinary mice the ability to see in near-infrared.

Credit: Pixabay.

“When we look at the universe, we see only visible light,” said Gang Han, the project’s principal investigator and a researcher at the University of Massachusetts Medical School.

“But if we had near-infrared vision, we could see the universe in a whole new way. We might be able to do infrared astronomy with the naked eye, or have night vision without bulky equipment.”

We are able to see because rods and cones — photoreceptor cells in the retina — absorb photons of light and send corresponding electric signals to the brain. But not all light is absorbed due to the fact that some wavelengths are too short or too long.

Most mammals, including people, can only see in a narrow range of the electromagnetic spectrum, called visible light. The visible spectrum extends from 380 nanometers to 740 nanometers, which is outside the infrared spectrum whose wavelengths extend from 800 nanometers all the way one millimeter.

In order to ‘see’ objects that give off infrared light, we had to invent specialized devices such as telescopes or thermal cameras. The latter, for instance, are equipped with detectors that can translate infrared radiation by assigning each temperature a shade of a color. Colder temperatures are often given a shade of blue, purple, or green, while warmer temperatures can be assigned a shade of red, orange, or yellow.

But would it be possible to detect infrared without any equipment? The researchers at the University of Massachusetts Medical School seem to think so.

Nanoparticles (white) bind to rods and cones in the retina of mice, allowing the rodents to sense infrared. Credit: Current Biology.

For their study, Han and colleagues injected a special type of nanoparticles called upconversion nanoparticles (UCNPs) into the eyes of ordinary mice. The nanoparticle solution contains the rare-earth elements erbium and ytterbium, which can convert low-energy infrared photons into higher-energy green light that is visible.

In order to test whether the mice could truly detect infrared, the researchers devised a series of physiological and behavioral tests.

During one such test, the mice were placed in a Y-shaped tank of water, where one of the branches had an opening through which the rodents could escape. The escape route was marked with visible light in the shape of a triangle, while the other blocked end was signaled with a similarly lit circle.

After a couple of rounds of training, the visible light was replaced with near-infrared.

“The mice with the particle injection could see the triangle clearly and swim to it each time, but the mice without the injection could not see or tell the difference between the two shapes,” says Han.

A single injection of nanoparticles in the eyes of the mice bestowed infrared vision for up to 10 weeks. Although there was a minor side effect (a cloudy cornea), it disappeared in less than a week. Tests found no damage to the retina’s structure, suggesting that the procedure is safe.

However, before the same could be done to humans, there’s still a lot of work to do. For one, there are biocompatibility uncertainties since the UCNPs are inorganic. Han would like to replace them with organic dyes instead of rare-earth elements.

 “We’ve shown that we can make organic UCNPs with much improved brightness compared with the inorganic ones,” he says. 

Besides enabling human beings to see beyond our natural capabilities, the procedure could be useful in medicine to correct human red color vision deficits or to trigger drug release upon contact with infrared light.

The researchers will present their findings at the American Chemical Society (ACS) Fall 2019 National Meeting & Exposition.

Rodents race around cage in NASA microgravity experiment

Humanity dreams of one-day becoming an interstellar species. But before that happens many challenges need to be addressed. Studies have shown that long-stretches of exposure to space can have important consequences for the health of astronauts. For instance, astronauts stationed aboard the International Space Station (ISS) have reported muscle and bone loss, poorer vision, DNA and brain structure alteration, and other effects. In order to better understand how space affects basic biology, NASA has performed over a dozen experiments with mice on the ISS since 2014. The most recent findings suggest that rodents are well accustomed to life in microgravity — and have even learned to do some nifty tricks.

Rodent astronauts

A small group of mice spent 37 days in microgravity — which is equivalent to a long-duration mission (18 months) given a rodent’s lifespan — inside NASA’s Rodent Hardware System, which is basically a high-tech cage. The rodent space habitat was specially designed to accommodate mice in groups, in order to reduce stress and better record the motions of the animals. Unlike previous space habitats, NASA’s most recent version also included grates on its wall which the rodents could grab onto.

NASA scientists focused on observing the behavior of the rodents, looking for anything peculiar. When compared to mice that stayed on Earth, the space mice were remarkably similar. The mice behaved as they normally would: feeding, grooming their fur, huddling together, and interacting with their peers. By the end of the study, space mice weighed about the same as their Earth counterparts and their fur was in excellent condition, both signs of good health.

NASA’s Rodent Habitat module with both access doors open.
Credits: NASA/Dominic Hart.

The rodents aboard the ISS quickly adapted to their environment, anchoring themselves to the habitat walls with their hindlimbs or tails and stretching out their bodies. The same pose is commonly employed by mice on Earth, which stand up on their back legs to explore their surroundings.

“Behavior is a remarkable representation of the biology of the whole organism,” said April Ronca, a researcher at NASA’s Ames Research Center and lead author of the study published in the journal Scientific Reports. “It informs us about overall health and brain function.”

Space mice also exhibited some remarkable, never-before-seen behavior. The experiments included both younger and older mice, and it seems like the younger mice would sometimes run laps around the cage, an activity which NASA scientists have called “race-tracking”.

Researchers aren’t sure what spurred this behavior, although some reasons may be for physical exercise, as a response to stress, or for stimulation of the body’s balance system which is thrown off by microgravity. Future experiments in space involving mice will now have to take into consideration the increased blood flow due to the extra activity.

Far from feeling threatened or stressed, these mice seem to be enjoying living in space.

“Our approach yields a useful analog for better understanding human responses to spaceflight, providing the opportunity to assess how physical movement influences responses to microgravity,” the researchers concluded in their paper.

Green tea and carrot compounds reverse Alzheimer’s symptoms in mice

Credit: Pixabay.

Billions have been spent on research that might lead to new drugs for treating Alzheimer’s, but while substantial progress has been made, there’s not much yet in the way of a cure. But one new study suggests that dieting may be an important factor for managing the neurodegenerative disease’s symptoms. According to the findings, chemical compounds typically found in green tea and carrots reversed Alzheimer’s-like symptoms in mice.

“You don’t have to wait 10 to 12 years for a designer drug to make it to market; you can make these dietary changes today,” said senior author Terrence Town, a professor of physiology and neuroscience at the University of Southern California. “I find that very encouraging.”

Town and colleagues focused on two compounds: EGCG ( epigallocatechin-3-gallate), one of the main ingredients of green tea, and FA (ferulic acid), commonly found in carrots, tomatoes, rice, wheat, and oats. The researchers randomly assigned 32 mice, which were genetically modified to have Alzheimer’s, to one of four groups, divided into an equal number of males and females. For three months, mice were given a combination of EGCG and FA, either EGCG or FA only, or a placebo — yes, rodents also have the placebo effect. Additionally, a group of healthy mice provided baseline performance for Alzheimer’s-free symptoms.

Before and after the three-month diet, the rodents were subjected to a barrage of tests that gauged their thinking and memory skills. One such test involves a Y-shape maze in order to assess a mouse’s spatial working memory, which is key to finding your way out of a building.

A healthy mouse will explore each arm of the Y maze in search of food or a way out. They will enter the three arms in sequence more often than by chance alone. But rodents with Alzheimer’s-like symptoms don’t do this as well because their spatial memory is impaired, making them more likely to explore the same arm twice.

“After three months, combination treatment completely restored spatial working memory and the Alzheimer’s mice performed just as well as the healthy comparison mice,” Town said.

Alzheimer’s disease is widely believed to be caused by the accumulation of beta-amyloid proteins which clump together to form plaques between neurons and disrupt cell function. Another physical characteristic of the Alzheimer’s diseased brain is the buildup of tau proteins, which tangle inside neurons, blocking their transport system. Town suspects that the compounds prevent bigger amyloid proteins from breaking up into smaller amyloid beta proteins that clog neurons. They may also reduce neuroinflammation and oxidative stress in the brain, both important aspects of Alzheimer’s pathology.

But while the study is exciting, its findings apply to mice and most such discoveries never translate into human treatments. Even so, green tea and carrots are harmless and there’s nothing to stop people from including them in their diet. In the future, Town wants to explore this combination treatment further.

The findings appeared in the Journal of Biological Chemistry.

Singing mouse.

The brains of singing mice might hold the secret of how we engage in conversation

Singing mice from the cloud forests of Costa Rica could help us better understand how our brains handle speech.

Singing mouse.

Image credits NYU School of Medicine.

The male Alston’s singing mouse (Scotinomys teguina) is quite the skillful bard. These tiny mammals can produce songs from a repertoire of almost one hundred audible noises and a host of sounds we can’t even perceive. There’s also surprising structure to their musical interactions — much like humans engaged in conversation, the mice challenge their competitors by singing in turn, a new paper explains.

The brains of these mice can help us understand the brain mechanisms that underpin our own ability to converse with one another. We tend to take this ability pretty much for granted, but it’s nowhere near widespread in nature, the paper notes. Standard laboratory mice, for example, produce ultrasonic sounds without evident timing of exchanges.

I talk, then you talk, and that’s our, communication hack

“Our work directly demonstrates that a brain region called the motor cortex is needed for both these mice and for humans to vocally interact,” says senior study author Michael Long, PhD, an associate professor of neuroscience at the New York University (NYU) School of Medicine.

Evolution has separated the duties of sound production and control circuits (i.e. those that handle the timing of replies) in the brains of singing mice, the team reports. This is similar to what is seen in crickets, some species of birds, and “possibly human discussion”, adds study co-first author Arkarup Banerjee, a post-doctoral researcher in Long’s lab.

The findings are based on electromyography measurements which the team performed on singing mice, meant to determine the relationship between different brain centers and muscular contractions. The readings were performed on two mice which coordinated their responses.

It’s an exciting find, the team adds, as we simply don’t have suitable mammalian models for the study of back-and-forth communication in the wild. A lot of animals engage in vocalization, sure, but their communication is more similar to a chatroom where everybody is talking at the same time than a balanced conversation. Up to now, they explain, the most reliable animal model neuroscientists could use to study vocal exchanges was the marmoset (family Callitrichidae), but it, too, came with significant limitations: their conversational turns are very slow compared to human speech, and unlikely to result from the fast muscle response to sensory cues, the team notes.

And no hard feelings, marmosets, but that just doesn’t cut it:

“We need to understand how our brains generate verbal replies instantly using nearly a hundred muscles if we are to design new treatments for the many Americans for whom this process has failed, often because of diseases such as autism or traumatic events, like stroke,” says Long.

The team found that the brains of singing mice come equipped with specialized areas that control how their muscles create specific notes. Separate circuits in the motor cortex enable the fast starts and stops that form a conversation between vocal partners. The former areas allow these mice to create the actual sounds, while the latter control their timing to prevent a cacophony.

Mice’s songs also change in social situations as individuals “bend and break the songs” to converse. They also report finding a functional “hotspot” in the side of the front of the motor cortex — the orofacial motor cortex or OMC — that regulates song timing.

In the future, the team plans to apply the mouse model to guide similar exploration of human speech circuits. They hope that understanding how two brains engage in conversations can help us identify what goes wrong in the context of disorders that interfere with communication, and even finding cures.

The paper ” Motor cortical control of vocal interaction in neotropical singing mice” has been published in the journal Science.

Nanaoparticles (white) bind to rods and cones in the retina of mice, allowing the rodents to sense infrared. Credit: Current Biology.

Scientists give mice infrared vision (and humans could be next)

Credit: Public Domain.

In something that seems out of a Philip K. Dick novel, researchers injected a nanoparticle solution into the eyes of mice, granting them the ability to see in infrared. Normally, the eyes of rodents, or humans for that matter, cannot perceive infrared electromagnetic radiation, although they can sense it in the form of heat.

Super vision

Most mammals, including people, can only see in a narrow range of the electromagnetic spectrum, called visible light. The visible spectrum extends from 380 nanometers to 740 nanometers, which is outside the infrared spectrum whose wavelengths extend from 800 nanometers all the way one millimeter.

“When light enters the eye and hits the retina, the rods and cones–or photoreceptor cells–absorb the photons with visible light wavelengths and send corresponding electric signals to the brain,” Gang Han at the University of Massachusetts Medical School, said in a statement. “Because infrared wavelengths are too long to be absorbed by photoreceptors, we are not able to perceive them.”

Infrared or thermal cameras are equipped with detectors that can translate infrared radiation by assigning each temperature a shade of a color. Colder temperatures are often given a shade of blue, purple, or green, while warmer temperatures can be assigned a shade of red, orange, or yellow.

We don’t know how exactly the mice in this experiment perceived infrared through their vision, but what seems likely is that they could.

Researchers at the University of Science and Technology in China and the University of Massachusetts Medical School developed nanoparticles that bind to the eye’s existing structures. Once the nanoparticles anchor to photoreceptor cells, they act as tiny infrared light transducers. When infrared light hits the retina, the longer infrared wavelengths are re-emitted into shorter wavelengths within the visible light range. So, technically, the mice don’t really see infrared — they see infrared information in a perceptible form, which is exactly how a thermal vision camera works.

“In our experiment, nanoparticles absorbed infrared light around 980 nm in wavelength and converted it into light peaked at 535 nm, which made the infrared light appear as the color green,” said Jin Bao at the University of Science and Technology of China.

Nanaoparticles (white) bind to rods and cones in the retina of mice, allowing the rodents to sense infrared. Credit: Current Biology.

Nanoparticles (white) bind to rods and cones in the retina of mice, allowing the rodents to sense infrared. Credit: Current Biology.

Mice injected with the nanoparticles showed various signs that they were able to detect infrared, such as their pupils constricting. In an experiment, the mice were able to navigate a series of maze tasks — which their normal-vision peers could not — showing that they could simultaneously sense both infrared and visible light.

A single injection of nanoparticles in the mice’s eyes bestowed infrared vision for up to 10 weeks. Although there was a minor side effect (a cloudy cornea), it disappeared within less than a week. Tests found no damage to the retina’s structure, suggesting that the procedure is safe.

Illustration of the infrared-to-visible-light conversion process. Credit: Cell.

Illustration of the infrared-to-visible-light conversion process. Credit: Cell.

“In our study, we have shown that both rods and cones bind these nanoparticles and were activated by the near infrared light,” says Xue. “So we believe this technology will also work in human eyes, not only for generating super vision but also for therapeutic solutions in human red color vision deficits.”

“In the future, we think there may be room to improve the technology with a new version of organic-based nanoparticles, made of FDA-approved compounds, that appear to result in even brighter infrared vision,” says Han.

In the future, the researchers plan to tweak their nanoparticles to better suit human eyes, which have more cones and rods than mice.

“This is an exciting subject because the technology we made possible here could eventually enable human beings to see beyond our natural capabilities,” says Xue.

The findings appeared in the journal Cell.

Credit: Pixabay.

Scientists regrow hair cells in mice, suggesting hearing loss is reversible after all

Credit: Pixabay.

Credit: Pixabay.

Hearing loss affects millions of people worldwide — a common health problem caused by noise, aging, disease, and heredity. Once a person loses part or all of their hearing, they cannot restore it. But is hearing loss really permanent? Not so fast, says a new study, which found that activating a certain signaling pathway caused mice to regrow hair cells.

Approximately one in three people between the ages of 65 and 74 has hearing loss, and nearly half of those older than 75 have difficulty hearing.  The most common type is sensorineural hearing loss caused by the degradation and loss of sensory hair cells in the cochlea (the auditory part of the inner ear).

Hair cells are the sensory receptors for both the auditory system and the vestibular system in our ears — and the ears of all vertebrates. They play a big part in both our hearing and our balance, transforming the sound vibrations in the cochlea into electrical signals which are fed up to auditory nerves and sent up to the brain.

If you’re a bird or frog, then you are able to regenerate hair cells. Unfortunately for humans, and all other mammals, we don’t have this ability.

“We’re the only vertebrates that can’t do it,” said Jingyuan Zhang, a researcher at the biology department at the University of Rochester, and co-author of the new study published in the European Journal of Neuroscience.

Zhang and colleagues wanted to find out whether they could treat the mammalian body into growing hearing cells, just like all other non-mammals can. They zoomed in on a group of epidermal growth factor (EGF) receptors that are known to be responsible for activating support cells in the auditory organs of birds. Once these cells are activated, they foster the generation of new sensory hair cells.

Mice, and likely all other mammals, express EGF receptors throughout their lives but are, nevertheless, unable to regenerate hair cells. The researchers at the University of Rochester have a hunch that during mammalian evolution, the expression of intracellular regulators of EGF receptors changed somehow, altering the signaling pathway. What if they could switch this pathway? That’s the million dollar question.

The team tested their theory by targeting a specific receptor called ERBB2 in cochlear support cells. In experiments, researchers used different methods to target the receptor, including a virus, drugs originally developed to stimulate stem cell activity but which are also known to activate ERBB2 signaling, and genetic modification of the mice themselves.

Activating the ERBB2 pathways unleashed a cascade of cellular events which eventually led to the proliferation of cochlear support cells, triggering neighboring stem cells to develop into new sensory hair cells.

“This research demonstrates a signaling pathway that can be activated by different methods and could represent a new approach to cochlear regeneration and, ultimately, restoration of hearing,” said says lead author Patricia White, research associate professor in the University of Rochester Medical Center (URMC) Del Monte Institute for Neuroscience.

Repairing hearing is a complex problem. Not only do hair cells require regeneration, but they also have to connect properly to the necessary network of neurons. But the findings are definitely promising, suggesting that sometime in the future, growing old may not necessarily mean you’ll have bad hearing anymore.

 

Wooden Figure belly ache.

Cannabis does reduce intestinal inflammation, and now we know why

New research on mice shows that endocannabinoids help prevent — or control — intestinal inflammation. These findings suggest that such compounds might serve the same function in humans.

Wooden Figure belly ache.

Image credits Wolfgang Claussen.

Cannabis users have long reported that the drug helps reduce the symptoms of inflammatory bowel disease (IBD). New research published by a team from the University of Massachusetts Medical School and the University of Bath explored why. Their findings reveal a novel mechanism that governs inflammation of the gut and may result in a new class of drugs to treat diseases that involve intestinal inflammation.

Pot gut

“There’s been a lot of anecdotal evidence about the benefits of medical marijuana, but there hasn’t been a lot of science to back it up,” said Beth A. McCormick, PhD and paper co-author.

“For the first time, we have an understanding of the molecules involved in the process and how endocannabinoids and cannabinoids control inflammation. This gives clinical researchers a new drug target to explore to treat patients that suffer from inflammatory bowel diseases, and perhaps other diseases, as well.”

While reports of marijuana helping alleviate gut inflammation are quite numerous, evidence to explain why aren’t. This study is the first to identify a biological mechanism that underpins this effect, helping to explain why cannabis reduces intestine inflammation for conditions such as ulcerative colitis and Crohn’s disease.

According to the team, gut inflammation is regulated by two distinct processes that each act in turn depending on the conditions in the intestinal environment.

The first process (which was identified in previous research) kick-starts an aggressive immune response in the intestine. This helps our bodies eliminate pathogens, but overzealous immune cells can also damage the lining of the gut by attacking cells indiscriminately.

The second process turns off this inflammation response. The response is spread by special molecules that move across the epithelial cells in the intestine (i.e. the lining) via the same channels that help flush out toxins from the gut.

The key here is that this second process involves a molecule called an endocannabinoid — which is very similar to the cannabinoids found in cannabis. If there aren’t enough endocannabinoids, inflammation won’t shut down and the body’s immune cells run amok on our guts’ lining.

McCormick and colleagues believe that because cannabis use introduces cannabinoids into the body, these molecules might help relieve gut inflammation as the naturally produced endocannabinoids normally would.

“We need to be clear that while this is a plausible explanation for why marijuana users have reported cannabis relieves symptoms of IBD, we have thus far only evaluated this in mice and have not proven this experimentally in humans,” she adds.

However, the team hopes that these findings will result in new drugs to help treat bowel diseases in humans.

The paper “Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis” has been published in the Journal of Clinical Investigation.

Credit: MELISSA HARRIS, UAB.

Gray hair linked to immune system activation in mice

Credit: MELISSA HARRIS, UAB.

Credit: MELISSA HARRIS, UAB.

Scientists at the National Institutes of Health and the University of Alabama at Birmingham found a link between graying hair in mice and the activation of the innate immune system. Specifically, the authors of the new study identified a connection between genes associated with hair color and genes that sound the alarm in the event of a pathogenic infection. The findings might explain why some people’s hair turns gray in response to chronic stress or some serious illness.

Our hair is colored thanks to melanocyte stem cells found in the hair follicle. When old hair falls, leaving room for new hairs to grow, the melanocyte stem cells serve as a reservoir of melanocytes — cells that produce a pigment called melanin. Without these stem cells, hair simply grows unpigmented, gray-colored.

Melissa Harris, Ph.D., assistant professor within the Department of Biology, along with colleagues at UAB, studied the genetic modifiers of hair graying in mice but also performed a transcriptomic analysis of melanocyte stem cells. This way, the team of researchers found a link between the transcription factor MITF and innate immunity.

MITF has a role in regulating the functions within melanocytes. One of these roles is keeping interferon response in check. Interferons are signaling molecules which are produced by cells when they detect a foreign invader. Interferons then signal to other cells to express the genes that inhibit viral replication. When MITF’s control of the interferon response was lost in the melanocyte stem cells, the mice’s hair turned gray. What’s more, in an experiment with mice that are predisposed for getting gray hair, when the innate immune signaling was activated, the number of gray hairs increased.

“Our lab uses some pretty cool genomic tools to take a broader look at how our cells change the way they function under different conditions. We focus on gene expression, and it used to be that we would have to focus on looking at one gene at a time, or a handful of genes. Now we can ask how the whole system changes its gene expression in one fell swoop. And sometimes this leads to discoveries that you do not expect! For instance, in this story, the fact that MITF represses the expression of interferon-stimulated genes. With our current day genomic tools, you don’t have to be limited by your own imagination!” Harris told ZME Science.

Credit: PLOS Biology.

Credit: PLOS Biology.

The findings suggest that the same genes that control pigment in hair and skin also control the immune system, possibly with important consequences in medicine. For instance, the connection might help researchers understand pigmentation diseases like vitiligo, which causes discolored skin patches and affects 0.5-1% of the population.

“For melanocyte-related disorders, we think this discovery will be relevant to our understanding of the autoimmune hypopigmentation disorders, vitiligo, and to the melanocyte-specific cancer, melanoma. Many vitiligo researchers have already speculated a role for innate immunity in the etiology of vitiligo, and this is just another step towards identifying mechanisms that could initiate vitiligo. In regards to melanoma, our studies could provide one example of how melanoma cells could mediate immune evasion. It’s become pretty well appreciated that tumors can evade immunosurveillance. If melanoma cells take advantage of the fact that MITF can repress aspects of the immune response, then this may contribute to their ability to ‘hide’ from the protective effects of our immune system,” Harris said.

It may also be possible that the findings can explain why some people experience premature graying of their hair as a result of illness or stress. The researchers aim to address this question in future studies.

“We would love to test whether the mechanism in this study could explain those anecdotal stories where people experience premature gray hair. Could the combination of a genetic predisposition and an every-day viral infection be just enough to negatively affect the melanocytes and melanocyte stem cells in humans, and cause early hair graying?” said Harris.

Scientific reference: Harris ML, Fufa TD, Palmer JW, Joshi SS, Larson DM, Incao A, et al. (2018) A direct link between MITF, innate immunity, and hair graying. PLoS Biol 16(5): e2003648. https://doi.org/10.1371/journal.pbio.2003648.

Credit: Pexels.

NYC mice are crawling with antibiotic-resistant bacteria and viruses

Credit: Pexels.

Credit: Pexels.

Rats get all the bad rep in New York City but it’s their smaller, more low-key cousins that could be far more dangerous pests. According to a new study, mice living in the basements of New York City apartments carry some bacteria and viruses that haven’t been seen before. What’s more, some of the bugs are resistant to antibiotics.

Of mice and bugs

Researchers at Columbia University collected feces from more than 400 mice captured over a period of one year in buildings in Manhattan, Brooklyn, Queens, and the Bronx. Most of the mice were caught in or around garbage disposal areas in sub-basements, though five mice were trapped in the food preparation/storage areas of a commercial building, and a single mouse was captured in somebody’s apartment.

The findings were reported on in two separate studies. The first, published in the journal mBio (the journal of the American Society for Microbiology), found that the rodents carried previously unseen viruses, as well as bacteria capable of causing life-threatening illness in humans. When they focused on the bacteria more closely, researchers detected several famous disease-causing pathogens like Shigella, Salmonella, Clostridium difficile, and E. coli. 

The most worrisome part of this study was the fact that some of these bacteria were antibiotic-resistant, similarly to those that have become nearly untreatable in area hospitals.

“From tiny studios to penthouse suites, New York City apartments are continually invaded by house mice,” says lead author Simon H. Williams, BSc, a research scientist at the Center for Infection and Immunity. “Our study raises the possibility that serious infections—including those resistant to antibiotics—may be passed from these mice to humans, although further research is needed to understand how often this happens, if at all.”

Salmonella infections are generally a result of eating food contaminated with animal waste — including mouse feces. In the U.S. alone, there are about 1.4 million reported cases of Salmonella infections annually along with 15,000 hospitalizations and 400 deaths.

The second study, also published in mBio, provides a detailed look at viruses present in the mice droppings. The mice carried 36 viruses, six of which are completely new to science. Fortunately, none of the identified viruses are known to infect humans. On the other hand, researchers identified genetic sequences matching viruses that are known to infect dogs, chicken, and pigs. This suggests that some of these viruses may have crossed over from other species — and if they did once before, they might do it again.

“New Yorkers tend to focus on rats because they are larger and we see them scurrying around in streets or subways; however, from a public health vantage point, mice are more worrisome because they live indoors and are more likely to contaminate our environment, even if we don’t see them,” says senior author W. Ian Lipkin, MD, senior author of both papers, John Snow Professor of Epidemiology, and director of CII.

Despite the numerous disease-carrying pathogens, the mice were generally healthy, signaling they’re carriers that are not affected by the bacteria. It’s unclear at this point how much of a threat these mice pose to people, or whether they’ve caused any human disease. The latter part would be impossible to prove by any research, in any case — the source of a patient’s infection is rarely investigated and they are not usually asked about any contact with mice. The real takeaway, according to Lipkin, is that “these things are everywhere.”

It’s also unclear whether the mice acquired these antibiotic-resistant bacteria from people — for instance, by eating food contaminated with feces from a person who was taking antibiotics — or whether the bacteria developed the resistance to the bacteria after exposure to discarded antibiotics. Despite that the source of the resistance is unknown, what’s certain is that the NYC mice harbored bacteria with 22 different genes that could confer resistance to a number of common classes of antibiotic drugs, including the quinolones, macrolides, and ß-lactams.

“These antibiotic resistance genes are out there in the environment and mice are carrying them everywhere,” Lipkin said. “My concern is that they are a reservoir of antibiotic resistance.”

Overall, the researchers found that more than a third (37%) of the mice carried at least one potentially pathogenic bacterium and almost one quarter (23%) of the mice harbored at least one antimicrobial resistance gene in their fecal bacteria. 

“We used to think of mosquitoes as the source of just an itchy bite, but now we know they carry Zika virus and West Nile virus,” says Lipkin. “We should be thinking of mice in the same way, as potential sources of infection. And that means we should control them as vectors of disease.”

Mouse.

Mice will pick social rules over might-makes-right, hinting at the birth of human societies and laws

Living in a group can be a hard thing to navigate, especially as an individual’s short-term interest can conflict strongly with the group’s long-term interests. A new paper looks into how mice juggle costs and benefits in social settings, with implications for other animals and humans as well.

Mouse.

Image via Pixabay.

People have learned to live together in huge communities, and a big part of that is solving conflicts through compromise and by following rules, instead of making justice with one’s fists. The sheer scale and complexity of the frameworks of rules we use to guide these resolutions, as well as our heavy reliance on cooperation, sets us apart from other animals.

Still, this also raises a question. How did this web of rules and cooperation evolve, and can other animals set up new social rules to help guide their interaction? A new study from the Center for Cognition and Sociality, part of the Institute for Basic Science (IBS), shows that lab mice can establish and then follow rules that are equitable (provide equal rewards in the long-term) even if they have to exercise patience and tolerance in the short-term. The findings provide a glimpse into how humans and other animals weigh costs and benefits in social interactions.

I don’t make the rules I just work here

Competition can be a powerful tool to getting what you want and need. But it’s also a very risky, one-against-all strategy, which comes with great costs both of time and of energy. With that in mind, humans generally adopt rules to guide how people with conflicting interests solve their differences without having to resort to aggression. The ‘first-come, first-served’ approach, or territorial ownership, are examples of such rules that, in the long-term, maximize the mutual benefit of everybody involved.

Other species also follow such rules. Some species of social spiders, the team notes, will back away when trespassing on someone else’s territory and will look for an unoccupied place. Rodents, however, are known to be impulse-driven, especially when food is concerned. A mouse would rather eat a small amount of food now than wait for a large serving later. Chow, after all, is a matter of survival.

However, the IBS researchers were curious to see how well-fed mice would behave when presented with a less immediate and necessary reward — could they learn to adapt to new social rules to maximize the rewards for all involved?

In lieu of food, the team used headsets that could produce a wireless electrical brain stimulation (WBS) in the medial forebrain bundle, the brain’s reward circuitry. The mice would feel this as a very powerful (yet nonaddictive) sense of pleasure, which they tend to prefer even over mating, as previous work revealed.

The mice were then trained using a specially designed box. It had a starting area in the center, and two reward zones to its left and right. The animals learned to start the round by entering the central area, and then follow a blue light indicating one of the reward zones. The light was randomly allocated and indicated where a mouse had to go to receive a five-second WBS pleasure-burst.

For the experiment, the team first placed two trained mice in the same box, setting them up for a winner-takes-all scenario. The mice had to further learn that the round only started when both entered the start zone together. Moreover, they had to figure out that only the first mouse to enter would receive the WBS — as soon as the second one entered the same zone, the signal was interrupted.

Cooperation rules

Over time, the researchers report, mice developed a “social rule” through which to split up the box. One mouse would only go for the pleasure doses on the left zone, while the other would only go for those on the right. Out of the 38 mice tested in this step, 23 (60%) observed the rule and waited for their turn. Those that respected the rule went through more rounds during the experiment than their peers, thus receiving more reward time overall. In other words, despite the initial effort of obeying the rules, teams of cooperating mice got more reward for each member than those who didn’t work together.

“Violating the rule is not a problem in the short term, but it is not sustainable in the long-term,” says Professor Shin Hee-Sup, corresponding author of the study. “Mice that respect the social rule learn how to play to their mutual advantage.”

However, he admits that the mice were still tempted to cheat the system and get some extra reward out of the situation. “From time to time,” even the most cooperating mice would, after waiting for a few seconds so as not to disrupt the other mouse’s WBS hit, “try their luck by going to the opponent’s territory,” Hee-Sup explains. Here is where another rule underpinning social cooperation comes into play.

“Another rule is tolerance. If a mouse violates the rule, the other mouse has the choice of retaliate immediately, or tolerate and keep on observing the rule. Tit for tat brings a disruption of the system, while tolerance to partner’s mistakes allows the system to continue, and as a result both mice receive a long-term benefit,” explains the professor. “This is called Bourgeois strategy in psychology. It limits aggression and is better for the long-term.”

Overall, rule observance increased over time during the test. This happened independently of the mice’s body weight or learning ability. To prevent habit (such as a mouse forming a preference for one side of the box) from biasing the results, the authors also swapped members between the teams to couple rats that had previously gone on the same side. Disoriented and confused at first, the animals quickly re-assigned territory, one going to the left and one to the right. This phenomenon is known as “rapid rule transfer,” and shows that mice are capable of adapting the same social rule to new situations.

In the future, the authors want to see if familiarity between the mice influences their tendency to observe the rules. Another interesting avenue of research would be to see if the mice keep following the rules in unfair conditions — i.e. when they’re trained to expect that the zones receive an equal amount of reward but that doesn’t happen.

The paper “Mice in social conflict show rule-observance behavior enhancing long-term benefit” has been published in the journal Nature Communications.

Mouse.

New York mice are actively evolving into a new species: city mice

New York city rats show early signs of speciating away from their rural peers, a new paper reports. The main cause is likely greater food availability and different nutritional make-up.

Mouse.

Image via Pixabay.

Stephen Harris, a PhD graduate at the State University of New York who will join the biology faculty in 2018 and Jason Munshi-South, associate professor of biological sciences at the Fordham University in New York City, say there’s nothing quite like a New York City mouse.

The duo captured 48 white-footed mice (Peromyscus leucopus) from three parks across the city and in three in nearby rural areas to see if they can find any signs of biological adaptation to city life. White-footed mice are native to this area of North America, so the team looked at more subtle changes, in particular, differences in gene expression. RNA analysis revealed that the urban mice show 19 single nucleotide polymorphisms (SNPs), areas in the genome where a single nucleotide (letter) is different between two individual or groups.

Several of the SNPs were located in genes tied to digestion and border metabolic processes. One of these is involved in the synthesis of omega-3 and omega-6 fatty acids and is a version of a gene humans seem to have selected as we were transitioning from hunter-gatherers to agriculture.

Cheeseburger hypothesis

The team also notes finding genes tied to non-alcoholic fatty liver disease, which they say can be indicative of the mice eating a lot of fatty acids — which fast food has in abundance. The mice also displayed larger livers with more scar tissue.

“The first thing that we thought of was the ‘cheeseburger hypothesis’: urban mice subsidizing their diet on human food waste,” says Harris.

Besides junk food and waste food, city mice can also get their paws on other tasty treats, like seeds, nuts, or berries growing in parks. These sources are also more plentiful than in rural areas, where higher inter-species competition limits their access to food. So the most likely thing happening here, Richardson says, is that the mice rely on a mix of urban foodstuffs, and occasionally dine on human food waste for a calorie boost.

The work is part of a wave of studies investigating examples of rapid adaptation, showcasing evolution in the works. However, the authors caution that their sample size was too small to draw any definitive conclusions at this point in time, so future studies will be needed to confirm or the results.

The paper “Signatures of positive selection and local adaptation to urbanization in white-footed mice (Peromyscus leucopus)” has been published on the preprint server bioRxiv.

Contagious scratching may be hardwired into the brain

A new study on itchy mice has revealed how this ‘socially contagious’ behavior spreads between individuals.

Image credits Efraimstochter / Pixabay.

Yawning is widely touted as being a contagious behavior — if you see someone yawning, the theory goes, you’re much more likely to yawn yourself. Itching seems to be another type of contagious behavior, for men and mice alike.

Of itching mice and men

Neuroscientists Zhou-Feng Chen from the Washington University School of Medicine, St. Louis, has provided the first conclusive evidence of scratching behavior spreading from mouse to mouse. He also worked to explain how it spreads, potentially giving neuroscientists the tools they need to understand how contagious behaviors function in humans.

So how do you make a mouse itch? Well, you show him other mice scratching, of course! Chen and his team housed normal mice in view range to particularly itchy littermates or showed them videos of itchy mice mid-scratch. Shortly after witnessing scratching or seeing it on videos, the subject mice started scratching themselves.

“Within a few seconds, the mouse in the enclosure would start scratching, too,” Chen said. “This was very surprising because mice are known for their poor vision. They use smell and touch to explore areas, so we didn’t know whether a mouse would notice a video.”

“Not only did it see the video, it could tell that the mouse in the video was scratching.”

By comparison, mice housed with fellows who wouldn’t scratch or who were showed videos of non-itchy mice looked at them with the same frequency as the first group, but rarely scratched immediately afterward.

It’s all in the brain

The team wanted to know what happened in the brains of mice witnessing scratching behavior from their fellows to make it contagious. So they monitored the brains of the group shown scratching and found that several spots displayed increased activity. But one particular cluster of nerves, the suprachiasmatic nucleus (SCN) which controls circadian rhythms, was highly active after they witnessed the behavior. The SCN was observed release a substance in response to this stimulus known as gastrin-releasing peptide (GRP) — which Chen previously identified as a key transmitter of itch signals between the skin and the spinal cord.

Image credits Yao-Qing Yu et al. (2017) / Science.

Rats who had the genes governing GRP synthesis or that of its receptor molecule inactivated didn’t catch the scratching behavior — but still scratched when they had their skin lightly irritated by the researchers. Furthermore, a dose of GRP injected into the SCN regions of normal mice caused them to scratch, but a dose of plain saline solution injected in the same spot didn’t.

“It’s an innate behavior and an instinct,” Chen added.

“We’ve been able to show that a single chemical and a single receptor are all that’s necessary to mediate this particular behavior. The next time you scratch or yawn in response to someone else doing it, remember it’s really not a choice nor a psychological response; it’s hardwired into your brain.”

While socially contagious itching is also present in humans, it’s still unclear how the findings translate to us. Our brain also has an SCN region, roughly behind the eyes — but so far, there’s no documented link between the SCN and contagious itching. What we know of the area tells us it should respond to changes in light to regulate circadian rhythms — it’s what makes your jet lag go away after a while — but those are relatively simple stimuli compared to scratching, which is very complex and much more subtle than overall light level.

Still, Chen’s research helps to offer a course for future research into the issue of contagious behaviors.

The full paper “Molecular and neural basis of contagious itch behavior in mice” has been published in the journal Science.

 

Scientists discover ‘hunting circuits’ that can turn fuzzy rats into fuzzy murderous rats

Two sets of neurons have been identified in the amygdala that, when activated, can turn mice into highly effective killers, a new study reports. The findings could help determine how hunting behavior evolved, hundred of millions of years ago.

Image credits Alexas_Fotos / Pixabay.

Here’s one the conspiracy theorists will love.

A team from Yale university have managed to hack the brains of mice into highly efficient killing machines. They ramped up the animals’ aggression by activating two sets of neurons in their amygdala, the paper states.

“The animals become very efficient in hunting,” says Ivan de Araujo, associate professor of psychiatry at Yale University and an associate fellow at The John B. Pierce Laboratory in New Haven.

“They pursue the prey [a live cricket] faster and they are more capable of capturing and killing it.”

Tampering with these neurons caused the mice to attack even inanimate objects — sticks, bottle caps, and an insect-like toy. Dr De Araujo says that the animals bit the toy “intensively” and even used “their forepaws in an attempt to kill it.”

Bloodlust, but with manners

The mice saved their aggressiveness only for prey, as De Araujo reports that the furry rodents didn’t attack one another even with both sets of neurons activated. These results offer a glimpse into how the brain changed hundreds of millions of years ago when jaws first developed. It was the first time any brain had an efficient tool with which to kill prey, a change that “must have influenced the way the brain is wired up in a major way,” De Araujo says.

Just like the military has a chain of command to make sure everything is where it’s supposed to be in battle, brains needed to re-wire to allow for specialized hunting circuits. These serve to govern and coordinate the movements of predators’ jaws and neck muscles, turning a clumsy beast into a deadly predator.

“This is a very complex and demanding task,” De Araujo says.

The team used mice since we know these animals are predatory — they hunt and eat whatever they can, really, mostly insects and worms. One species, in particular, is known as the killer mouse for its habit of feeding on live prey, even other mice at times.

By watching brain scans of hunting mice, they discovered one set of neurons that activated when chasing prey and another that would flare up when biting or killing something. Both of these bundles of neurons are located in the amygdala, which is involved in regulating emotion and motivation.

The next step was to use optogenetics to create mice in which these sets of neurons could be activated using a laser.

“When we stimulate [both sets of] neurons […] they assume the body posture and actions usually associated with real hunting

“It is as if there is a prey in front of the animal,” De Araujo says.

The team found evidence of similar “hunting circuits” in other species that relied on hunting to survive — including humans.

Knowing how the brain processes hunting and killing gives us a glimpse of how — and when — these behaviors evolved. It might also help us understand how aggression, in general, is handled by the brain.

The paper “Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala” has been published in the journal Cell.

elephant and mouse

Are elephants really frightened by mice?

elephant and mouse

Credit: TV tropes

From Saturday morning cartoons to fables, one of the most popular images we can find is that of an elephant cowering in front of a mouse. This conjuring is often used as an allegory for the underdog, but is there any truth to it?

Eek, a mouse!

It’s not clear where or when the first ‘elephant scared by a mouse’ myth started. One version can be traced back to 77 AD, the time of Pliny the Elder —  next to Aristotle, probably the most influential scholar in antiquity. Pliny was the first to say “the elephant hates the mouse above all other creatures,” and because he was so influential and highly regarded, this sort of stuck not only with the Romans but for millennia afterward. Remember, elephants didn’t live in the so-called ‘civilized Western world’ so like other exotic species, their appearance and behavior were left to the imagination. Just look at how people used to think elephants looked like in the Middle Ages — totally hilarious.

The myth wasn’t eaten whole by everyone, though. Some were rightfully intrigued by the imagery of a 3-ton-animal petrified by a teeny-weeny mouse, like Allen Moulin who was a physician during the 1600s. Moulin, who wasn’t very familiar with elephants but at least had some knowledge of their anatomy, reasoned that since elephants lack epiglottis — a cartilage that protects the windpipe while swallowing — then it reasonable to assume that such a big creature could be afraid of a tiny one if it could crawl up the elephant’s trunk and suffocate it.

Alas, like Pliny before him, Moulin wasn’t really on to anything. He did, however, perpetuate a seemingly scientific explanation for why the biggest land mammal in the world is afraid of mice.

Like any wildlife biologist will tell you today, elephants do have that flappy cartilage to protect their windpipes. Even if a mouse, insect or any kind of ‘debris’ ended up the trunk, the elephant needs only to blow it. In fact, that’s what they do most of the time when they feel the trunk is getting clogged.

Yet in an episode of Myth Busters, Adam Savage and Jamie Hyneman found the myth was actually ‘plausible’. Though they didn’t give it any chance, their experiments suggest that South African elephants stopped dead in their tracks when they were met by mice hidden in dung. Once the elephants noticed the little critters, they actually backed away and even started moving in the other direction.

According to John Hutchinson, who is a researcher at the Royal Veterinary College in London, elephants in the wild get nervous whenever a small but fast animal meets their tracks. That means that not only mice can frighten them, but dogs, cats and just about anything that’s agile. Also, there’s a novelty factor involved.

Captive elephants, like those in zoos or circuses, are often seen sleeping with rodents right on top of them. They seem to mind very little, as most keepers would tell you.

So, rather than being afraid of mice per se, elephants seem to be startled by frantic movements. And, really, the same can be said about any animal living in the wild.