Those Little Rats

Mother Love Makes Rats Smarter

If a farmer fills his barn with grain, he gets mice. If he leaves it empty, he gets actors.

- Sir Walter Scott

Behavioral psychology is the science of pulling habits out of rats.

- Dr Douglas Busch

Montreal teenagers who complain about overly protective mothers getting on their nerves might be on to something. Maternal care does have a measurable neurological effect - it appears to make young rats much more intelligent, according to a study conducted by Canadian researchers published in Nature Neuroscience.

Researchers led by Professor Michael Meany at McGill University in Montreal studied two groups of mother rats in a cross-fostering study. The behaviour of mothers in one group was characterised by an intense level of caring for their offspring, including licking, grooming and other interaction involving physical contact. Mothers in a comparison group seemed generally uninterested in their young beyond feeding them.

Both groups of young rats were made to perform a variety of tests once they were adult. The main task involved swimming through a floating labyrinth five times a day to look for a submerged object. The "mama's boys" - and girls - outperformed their peers, learning spatial relationships faster, retaining what they learned longer and exhibiting higher levels of curiosity and playfulness than their more neglected counterparts.

Researchers analysed the brains of these rats and discovered that the hippocampus, responsible for attention and memory, contained more synapses than were present in the other rats' brains. Since the neuronic development of rats is similar to that of humans, the researchers believe the results, in principle, may be extended to human beings. Mr Meany refuses, however, to link maternal care with moral proselytising, saying: "I don't think the issue here is about good or bad mothers.

"In nature, it's generally environmental influences that keep mothers from taking better care of their offspring - and when the young grow up - in an environment where food is scarce and enemies abound, it's perhaps better to be a little more afraid - then they don't find themselves in danger quite so easily." - PA

Source: The Dominion 24 July 2000

More: Cuddled Babies, Less-Stressed Adults

by E J Mundell

New York - Simply being touched and held during the first few years of childhood may set up positive stress-response patterns that last a lifetime, experts say. Studies in rats, conducted by researchers at Montreal's McGill University, have found that newborns who receive repeated touching, licking and grooming from their mothers have "all sorts of protective benefits against the negative effects of stress in adulthood," according to Darlene Francis, one of the Canadian researchers. A report of these findings appears Friday in the journal Science.

Francis says previous studies on rat mother-and-child behavior consisted of researchers removing pups from mothers for 15-minute periods each day. Upon their return to the mother, licking, grooming, and squealing ensued until mother and pup calmed down. What researchers discovered was that pups who underwent such temporary separations ended up with lowered stress responses in adult life. In the latest research, separations did not occur. Instead, groups of mothers with newborns were simply observed. "All we did was go in every hour and score what was going on," Francis explained. "Some mothers licked and groomed their pups more (than other mothers)."

Once the pups had reached adulthood, the Montreal researchers took measurements of various hormones known to mediate the stress response. They also examined each pup's hippocampus, an area of the brain thought to be involved in stress control. The investigators discovered that pups whose mothers had been especially attentive during childhood had more of a certain kind of receptor on the surface of the hippocampus than relatively "neglected" pups. These receptors responded specifically to the hormone corticosterone, which is secreted by the adrenal glands during stressful situations. Production of this hormone is shut down when the hormone binds to receptors on the hippocampus, and a signal is sent from the brain back to the adrenal gland, effectively telling it to "switch off" production. More corticosterone-receptors on the hippocampus of the "well-fondled" rats means the brain is more sensitive to the hormone, and more efficient in sending back this signal to stop the stress response.

The rats who received more mothering also had lower levels of the stress hormones in their blood. "So our handled animals, or in this case, the high licking-and-grooming animals, had less corticosterone release during times of stress," Francis explained. "And once the stress is finished they return to normal faster." But how similar are rats to humans? She says humans secrete cortisol, which is very similar to corticosterone. And while we don't lick and groom our newborns, most human parents do seem fond of holding and caressing them. "That's what we're presuming is the parallel in the human condition," Francis said.

The development effect seems to be time-specific, she said. The stress-reactions of rats in adulthood seem to be "programmed" by maternal touch during the first two weeks of life. Francis says this time period may be likened to the first 3 years of human development. She notes that, until recently, we had no human models to help verify if rat development was mirrored in homo sapiens. But the sad legacy of a fallen regime may have provided scientists with just such a model. Francis says Harvard researchers are studying the hormonal levels of Romanian orphans who were simply "left alone in cribs or playpens, with no stimulation, no interaction" for the first few years of life. The Harvard researchers "are finding similar measures," Francis says. "They're finding that their cortisol measures are really high," compared with similarly-aged children brought up in family homes. The plight of these orphans in later development has been well documented - distant, highly-stressed, insular children who have difficulty coping with "normal" human interaction and touch.

Francis says the Montreal researchers plan future studies to determine if the long-term emotional conditioning brought about by early childhood licking-and-grooming is "fixed" or malleable. One experiment will take pups partially-raised by relatively non-cuddling mothers, and place them with more tactile "foster" moms, to "see if we can modulate the stress response that way."

Taken from Science 1997 277:1859-1861

And Finally: Study Suggests Maternal Care Affects Later Adult Stress

Brighton, England - The way a mother cares for her baby can determine how stressed out the child will be as an adult because her nurturing can permanently change the way the infant's genes operate, new studies on rats suggest. The studies, presented Sunday at a conference on the fœtal and infant origins of adult disease, found that baby rats who were licked by their mothers a lot turned out to be less anxious and fearful as adults and produced lower levels of stress hormones than those who were groomed less.

The scientists found that the mothers' licking caused the baby's brain to crank up a gene involved in soothing the body in stressful situations. Several human studies have found an association between a mother's nurturing and the future mental health of her children. The rat research, led by Michael Meaney, a professor of medicine at McGill University in Montreal, Canada, for the first time rigorously tested whether it really is the mother's behaviour that makes the difference and showed what happens in the brain of the offspring to produce the adult characteristics.

However, it's unclear how the findings translate to humans, especially whether kissing and cuddling would be the equivalent behaviour, experts said. "That's where we start to become cautious," Meaney said. "In the rat, the key input is tactile, so it's very tempting to say tactile stimulation could do the same for humans, but we don't know that." Rats are born with their eyes closed and are very sensitive to touch, whereas humans are born into a more complex environment with a greater range of sensory stimuli, he said.

Experts said that while the details of what maternal behaviours are important in humans might differ, they suspect the general principle and mechanism will prove true. "This is a very important study. It's fabulous data - really world-class," said Peter Gluckman, a professor of pædiatric and perinatal biology at the University of Auckland in New Zealand, who was not involved in the research. "It shows us that the expression of genes in mammals can be permanently changed by how mothers and infants interact and how that can have long-term effects on behaviour and psychiatric health."

The study involved more than 100 rats in various experiments. "All the mothers nurture their pups, provide ample milk and the pups grow up perfectly well. But there is one behaviour, called licking and grooming, that some mothers do much more than others - four or five times as much," Meaney said. Meaney set out to test whether baby rats who are licked more turn out differently from those who are licked and groomed less and if so, why. "The pups who are licked more are less fearful, they produce less stress hormones when provoked and their heart rate doesn't go up as much, so they have a more modest stress response than the pups who are licked much less," he said.

The brain contains receptors for stress hormones such as cortisol. The more receptors there are, the more sensitive the brain is to cortisol and the easier it is for the brain to tell the adrenal glands when to stop cranking out the hormones. The receptors set the tone for how the body responds to stress. Meaney found that the rats who were reared with much licking had more cortisol receptors in their brains than the others and he determined why and how. He examined the DNA of about 50 rats who were licked a lot and another 50 who were not. "The receptors are made by genes. The gene was more active in adult rats who were reared by high-licking mothers than in those raised by low-licking mothers," he said.

To verify that it was the licking behaviour that was causing the difference and not inherited genes, the scientists swapped the babies and mothers around, so that offspring of mothers that licked a lot were given to low-licking mothers and vice versa. The results were the same - those who got licked a lot turned out to be less stressed out as adults, regardless of who their natural mother was, and the gene responsible for that cooler response was more active. The scientists even took the mothers out of the picture altogether and stroked the baby rats with paint brushes. "It does the same thing that maternal licking does," Meaney said. The change in the production of the brain receptors was apparent by the second week of life and could be reversed by chemical manipulation in the rats, which suggests the changes would not be irreversible in humans, Meaney said.

Why take a chance? Lick and fondle your pet rats today! No? Well at least have skin contact with your baby and/or toddler all you can. Trade your stroller for a baby carrier that you can wear like a backpack. The exercise will be good for you and your child may be less stressed as an adult. You will also probably grow closer and be better friends in later life.

Rats and Mice

Domestic rats have been raised in captivity for more than a century. They bear little resemblance to their wild ancestors. A pet rat is very clean, performing an elaborate grooming ritual several times a day: the rat first licks its front feet, or hands, then using both hands it washes its face and behind its ears.

Rats can be gentle, affectionate and intelligent pets. They rarely bite unless handled roughly so that they become frightened or in pain - but then can inflict a rather serious wound. Pick rats up by lightly placing your hand around the shoulders with the thumb under the animal's chin. Hold the animal firmly to prevent escape but do not hold so tightly as to injure it. If the animal appears aggressive, carefully grasp the tail at the base and gently lift it by the tail.

Some pet rat owners refer to rats as superpets because of their superb pet qualities. Pet rats are friendly and curious, intelligent, have good memories and enjoy human company. When your rats hear you come home or enter their room, they will greet you at the cage door eagerly waiting to come out and play. You can let one ride on your shoulder, carry it in a pocket, or tuck it in a sleeve. Your pet rat can learn its name and learn to come when called. Rats also make excellent classroom pets - they are not timid like mice, and unlike hamsters, rats rarely bite. A rat has excellent insight and the ability to solve problems. You can train them to perform clever tricks for treats.

If handled gently, mice can also make excellent pets. Mice will be amenable to their owner. In unfamiliar situations, however, they may bite so they should always be handled with care. The more mice are handled the better pets they will be. Mice should be picked up by the tail - NOT the tip, but gently grab at the middle of the tail. Set the animal on a rough surface, while holding the tail and allow it to stretch out. While it is stretched out, grab the scruff of the neck and release the tail.

Housing for rats and mice is similar to that of gerbils and hamsters but with special care to recognise their ability to open cage doors, eat through plastic and force lids off the top of their enclosure. Great care must be taken to prevent escape. Being omnivorous, they are easy to feed and good commercial diets are available.

Source: various sites on the internet

Is the World Ready for a Man-Mouse?

by Nicholas Wade

Researchers See Uses for Hybrids

New York - A group of American and Canadian biologists is debating whether to recommend conducting stem cell experiments that would involve creating a human-mouse hybrid. The goal would be to test different lines of human embryonic stem cells for their quality and potential usefulness in treating specific diseases. The best way to do that, some biologists argue, is to see how the cells work in a living animal. For ethical reasons, the test cannot be performed in people. But if the human stem cells were tested this way in mice, any animals born from the experiment would be chimeras - organisms that are mixtures of two different kinds of cells - with human cells distributed throughout their body.

Though the creatures would probably be mice with a few human cells obeying mouse rules, the outcome of such an experiment cannot be predicted. A mouse with a brain made entirely of human cells would probably be discomforting to many people, as would a mouse that generated human sperm or eggs. Dr Irving Weissman, a stem cell expert at Stanford University, said that making mice with human cells could be "an enormously important experiment," but if done carelessly, could lead to outcomes that are "too horrible to contemplate." He gave as an extreme example the possibility that a mouse making human sperm might accidentally be allowed to mate with a mouse that had made its eggs from human cells.

At least two biologists in the group discussing the experiment believe it is premature or unethical and could stir policymakers to limit further stem cell research or ban it. Stem cells, the clay from which all tissues of the body are generated, hold high promise as an all-purpose material for repairing many of the degenerative diseases of old age like Parkinson's, cancer and heart disease. Other scientists say such experiments would be of great value and could be conducted with human stem cells engineered so that they could not produce brain or reproductive cells. They acknowledged that even an experiment designed with such precautions should first undergo scientific review and public debate.

The proposal for the experiment grew out of a meeting held on 13 November at the New York Academy of Sciences. It was sponsored by the academy and by Rockefeller University and was organized by Ali Brivanlou, a Rockefeller biologist who studies embryology. Brivanlou invited eight other stem cell experts and, as observers, two scientific journal editors and Dr James Battey, director of the National Institute of Deafness and chairman of the stem cell task force of the National Institutes of Health. The meeting was not intended to be public, Brivanlou said, and at one stage the nine experts held a closed session at which the observers, including even Battey, were asked to step outside. One of the journal editors then wrote of the meeting in the current issue of Nature, reporting that Battey "criticised participants for what he regards as excessive secrecy."

Battey did not return calls to his office.

The purpose of the meeting, Brivanlou said in an interview Tuesday, was to discuss setting quality standards for several new lines, or colonies, of human embryonic stem cells being developed around the world. In one test they discussed, human embryonic stem cells would be injected into an early mouse embryo, when it was still a small ball of cells called the blastocyst. Scientists would then see if the human stem cells showed up in all the tissues of the mouse's body. This ability, known as pluripotentiality, is the hallmark of a true embryonic stem cell.

Injection into another mouse's blastocyst is the standard test for mouse embryonic stem cells, which, like human embryonic stem cells, are derived from a small pool of all-purpose cells a few days after the fertilised egg has started to divide. No one yet knows if human embryonic stem cells would survive at all in a mouse blastocyst. But if they did, and contributed to all the mouse's tissues, this would be a useful test for the many claimed human embryonic stem cell lines being developed around the world, Brivanlou said. But a participant, Janet Rossant of Mount Sinai Hospital in Toronto, said she did not consider the test necessary and that if the injected human cells made major contributions to the mouse, "I think that is something that most people would find unacceptable."

Weissman, who was not at the meeting, said the experiment could help scientists follow the behaviour of human cells with genetic diseases. Studying how the diseased human cells developed within a mouse could offer new insights for treating the disease. Weissman said that undesirable outcomes, like a mouse with a brain made of human cells, or a mouse that generated human sperm, could be avoided by deleting certain genes from the human embryonic stem cells before injecting them into a mouse blastocyst. But he added that such procedures should be carefully reviewed by a body like the National Academy of Sciences. "You must assure yourself and the public that it's ethical - it's not for scientists alone to decide," he said.

Source: iht.com Thursday 28 November 2002 from The New York Times

Another way to mix mice and men...

Taiwan Couples Eat Mouse Testicles to Conceive

Women in Taiwan have begun eating mouse testicles in a bid to get pregnant. The craze follows claims by several infertile couples that they conceived after eating dishes containing the organs. One couple, from the southern county of Pingtung, told how they were taken by a friend to a local restaurant to taste a dish made from the organs. They conceived their long-awaited baby about a month ago, after eating six kilograms of raw mouse testicles, the United Daily News reports. The couple had previously consulted western medical doctors but were not given the cause of their infertility.

Source: ananova.com Saturday 4 January 2003

World's Oldest Mouse Reaches Milestone Birthday

University of Michigan’s geriatric mouse colony helps scientists learn about human aging...

Yoda sniffing his cage mate, Princess Leia. Dwarf mice always are housed with larger females
to provide body warmth needed to protect smaller dwarf mice from freezing to death.

Ann Arbor, Michigan - Yoda, the world's oldest mouse, celebrated his fourth birthday on Saturday, 10 April 2004. A dwarf mouse, Yoda lives in quiet seclusion with his cage mate, Princess Leia, in a pathogen-free rest home for geriatric mice belonging to Richard A Miller, MD, Phd, a professor of pathology in the Geriatrics Centre of the University of Michigan Medical School. Yoda was born at the University of Michigan Medical School. At 1,462-days-old, Yoda is now the equivalent of about 136 in human-years. The life span of the average laboratory mouse is slightly over two years.

“Yoda is only the second mouse I know to have made it to his fourth birthday without the rigours of a severe calorie-restricted diet,” Miller says. “He's the oldest mouse we've seen in 14 years of research on aged mice. The previous record-holder in our colony died nine days short of his fourth birthday. 100-year-old people are much more common than four-year-old mice.”

Miller is an expert on the genetics and cell biology of aging. To study the aging process, he has developed strains of mice, derived from wild mice captured in Idaho, that live longer, stay smaller and age more slowly than ordinary mice. Although extremely low-calorie diets have been shown by other scientists to produce very long-lived mice, the genetic approaches used in Miller's laboratory achieve longevity without the need to restrict food intake. Miller's mouse colony also includes strains of mutant dwarf mice, developed at Jackson Laboratory, which are very small and long-lived. Yoda is the longest-living member of this unusual tribe.

Miller's geriatric mice are providing important clues about how genes and hormones affect the rate of human aging and risks of disease late in life. His current work focuses on identifying defects in T cells from aged mice that interfere with a normal immune response, and finding ways to reverse those defects.

Contact: Sally Pobojewski

Source: med.umich.edu photo credit: Richard Miller, University of Michigan Medical School

Yoda died less than two weeks after his fourth birthday. Maybe Princess Leia was too hot for him...

A Different Kind of Guinea Pig

Photo source: story.news.yahoo.com (AFP/HO)

A pair of guinea pigs belonging to a new species discovered by two German scientists in Bolivia. The species differs from its cousins by remaining faithful to one partner. Another special feature of the Muenster is that instead of rejecting the young, the male plays with his offspring, according to biologist Matthias Asher, who observed their behaviour in Bolivia. "The discovery was completely by accident," Sachser said.

Six years ago, his team imported guinea pigs from the Cochamba province of Bolivia and unsuccessfully attempted to cross them with animals from the university's laboratory in a bid to eliminate the blood complaints caused by inter-marriage. The experiment failed because the laboratory animals failed to mate - which alerted the scientists that these were no ordinary guinea pigs.

Source: story.news.yahoo.com

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