Tag Archives: mice

Research Roundup: March for Science, promising headway in stem cell treatments, new treatment for cystic fibrosis and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • On Saturday April 22nd, hundreds of thousands of people are expected to march in defense of science in cities around the world, including Washington DC, London, Paris. Toronto, Berlin and more. Speaking of Research has a history of holding rallies in defense of science, and we wish those who are attending events on Saturday the very best of luck. With science funding in many countries under threat, it is important that we all stand up and be counted.

SR-March

 “The March for Science champions robustly funded and publicly communicated science as a pillar of human freedom and prosperity. We unite as a diverse, nonpartisan group to call for science that upholds the common good and for political leaders and policy makers to enact evidence based policies in the public interest.”
https://www.marchforscience.com/
#MarchforScience

  • Stem cell treatment and transplant shows vision and promise. Using induced pluripotent stem cells, a Japanese man is the first human to receive reprogrammed stem cells from another human being as a means of treating macular degeneration — a form of blindness that affects 1% of all humans over the age of 50. Before this procedure made its way to humans, safety and efficacy trials in mice (.e.g., 1,2,3) and non-human primates were undertaken (e.g., 1,2,3) — although it is worth emphasizing that some have raised concerns about the stringency of Japanese preclinical regulatory process. Takahashi, the lead scientist behind this trial, stated that the surgery has gone well, but that success cannot be declared without further monitoring the fate of the transplanted cells.

    SR-StemCells

    Somatic stem cells exist naturally in the body. They are important for growth, healing, and replacing cells that are lost daily through wear and tear.  Source: University of Utah

  • A new study finds that exposure to low doses of antibiotics early in life can have long term consequences on behaviour in mice. Adding to a growing body of literature, this study found that low but clinically relevant doses of penicillin administered prenatally in mice can lead to lasting effects in both sexes on gut microbiota, immune functioning, and alters anxiety-like, social and aggressive behaviour. Concurrent supplementation with Lactobacillus rhamnosus JB-1 via drinking water prevented some of these alterations — potentially via alterations to the vagus nerve. Subsequent replication and extension of these findings needs to be undertaken, particularly in regards to the length of exposure and when exposure occurs (early or later in gestation or even postnatally). The authors of this study concluded that “these results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria.” This study was published in Nature Communications.
    SR-miceantibiotics
  • Humane endpoints for zebrafish released on the Humane Endpoint website at Utrecht University in English, Dutch and German. “A humane endpoint is the earliest indicator in an animal experiment of pain or distress in the animal. Researchers can use these indicators to avoid or limit pain and distress in laboratory animals.” Zebrafish are a commonly used as laboratory species and, for example, in the Netherlands, an average of 5000 experiments are performed on zebrafish each year. Consistent with the 3Rs, these guidelines contribute the refinement aspect of the 3Rs “since it teaches scientists, animal technicians and animal caretakers how to prevent unnecessary pain and distress in laboratory animals.” Access to this website is free and for further details on who can and how to access all content can be found here.

    Zebrafish_Sanger

    Zebrafish: Wellcome Trust Sanger Institute

  • Vaccination of prairie dogs planned in an effort to save the black footed ferret. Black footed ferrets are members of the weasel family and were brought to the brink of extinction in the 1960s due to habitat destruction. By the 1980s it was estimated that only 18 remained. Due to conservation efforts, there are now approximately 300 of these ferrets in the wild and a further 300 in captive breeding facilities. Approximately 90% of the diet of these ferrets are comprised of prairie dogs. However, because of the Sylvatic plague, prairie dogs living in the habitats of the black footed ferret are now in danger of being decimated and spreading this disease to the ferrets that eat them. To combat this problem, wildlife conservationists such as the USGS National Wildlife Center are planning to a vaccination campaign in specific habitats of the black footed ferret. This is a great example of the reach of biomedical research with vaccinations developed in animals being used to save other animals.
  • Potential new treatment for cystic fibrosis found. Cystic fibrosis is a progressive genetic disease that leads to persistent lung infections and limits the ability to breathe. In particular, it affects the Cystic fibrosis transmembrane conductance regulator (CFTR) gene. In addition, it can prevent the pancreas from releasing digestive enzymes due to the buildup of mucus. It affects approximately 70,000 people worldwide. These researchers investigated whether thymosin alpha 1 (Ta1) — a naturally occurring protein with an excellent safety profile in the clinic — can rectify some of the multiple tissue defects associated with cystic fibrosis. Using inbred mice, they found that this protein leads to reduced inflammation and increased CFTR maturation, stability, and activity — indicating that Ta1 has a strong potential to be a single-molecule therapeutic agent to treat and stop the progression of cystic fibrosis. This study was published in Nature Medicine.
SR-CF

Image courtesy of National Library of Medicne

Research Roundup: A new approach to treating Parkinson’s, designer pig organs, the benefits of dragon blood, and more!

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Scientists may have discovered a new way to treat Parkinson’s disease (PD), a devastating neurological disease that causes tremors, rigid muscles, and changes in speech. In PD, a person’s brain cells (neurons) die causing a reduction in the neurotransmitter, dopamine. Researchers in Sweden were able to reprogram human astrocytes – brain cells that normally support the functions of neurons – to behave more like dopamine producing neurons. They did this by bathing the astrocytes in a petri dish in a number of molecules that affect changes in the cell’s DNA. This proof of concept allowed researchers to take the next step and try this therapy in a mouse model of PD. Injecting the same cocktail of molecules into the brains of PD mice caused the astrocytes to become more like the dopamine producing neurons, and this change lessened the PD symptoms in the mice. Obviously, many more studies are needed before this potential therapy can be tried in human patients with PD, but this is an exciting advancement in our quest to treat this disease. This research was published in Nature Biotechnology.
animal testing, animal research, vivisection, animal experiment

Mice were key to this Parkinson’s breakthrough

  • A new study finds that a reovirus may be implicated in the development of celiac disease. Celiac disease is a serious autoimmune disease where the ingestion of gluten, leads to damage of the small intestine. Gluten is found in many common foods, and is the general name for wheat derived proteins. “It affects 1 in 100 people worldwide, and 2.5 million Americans are undiagnosed and are at risk for long-term health complications”. Mice, were infected orally with two derived forms of a human reovirus, T1L and T3D; both capable of infecting the hosts` intestine but affecting its functioning in different ways. They found that while mice were able to successfully clear the virus from the system; exposure to the virus can disrupt intestinal homeostasis, lead to a loss of oral tolerance to the antigens produced by the body, and promote immunopathology similar to the symptoms of celiac disease. This study will of course need to replicated and further research investigating other reoviruses and the subsequent link to the development of celiac diseases firmly established. This study, using mice, does however, provide hope for the millions of individuals suffering from celiac disease and if a strong link to reoviruses is established; can lead to the development of a vaccination. The research was published in Science.
  • A promising vaccination for Zika virus has been found, reducing the occurrence of congenital abnormalities in mice. Zika virus is an emergent global health threat, that is transmitted by mosquito bites and more recently it has been discovered that it can be passed on via sex with an infected person. The most debilitating effects of the virus are death in the young and elderly are with compromised immune systems and perhaps most strikingly birth defects — in particular, microcephaly; a sign of incomplete brain development. For the first time, these researchers tested a live attenuated version of the Zika virus in mice. In comparison to an inactivated vaccine, live attenuated vaccinations have the advantage of single-dose immunization, rapid and robust immune response, and potentially long-lived protection. They found that this live attenuated vaccination was able to confer sterilizing immunity (complete protection from infection), a robust T-cell immune response, and a promising safety profile; similar to that of other clinically approved vaccinations. This study was published in Nature Medicine.

Illustration of a baby with microcephaly (left) compared to a baby with a typical head size

  • A new study finds that the human body’s peripheral nervous system could be capable of interpreting its environment and modulating pain. The sensation and perception of pain has historically been associated with the brain and the spinal cord (central nervous system(CNS)) and drugs for pain target the CNS. However, these drugs sometimes lead to unintended side effects such as addiction and tolerance. Drugs which target the peripheral system may allows us to avoid these unintended side effects. Using mice, these researchers demonstrated that the peripheral nervous system was able to interpret the type of stimulation it was sensing, although further research is needed to figure out how these sensations are interpreted by the brain. While further replication and validation is needed, this study widens our view of pain, its sensation and potential means of treatment. This study was published in the Journal of Clinical Investigation.

  • Luhan Yang, Chief Scientific Officer at eGenesis, is working to create ‘designer pigs’ which could be used to help alleviate the organ crisis. By inserting up to 12 human genes into pig ova they hope to overcome the rejection problems which currently prevent xenotransplantation from providing viable organs for human use. Yang hopes the use of the gene-editing technique CRISPR will make it possible to create human-animal hybrid organs that can be used to save lives.

  • New study finds that variant of protein in komodo dragon blood (VK25) contains antimicrobials that may one day form the basis of a new antibiotic. Researchers at George Mason University synthesized a new molecule,DRGN-1, based on a peptide found in the blood of the Indonesian lizard. This molecule was shown to promote healing in mice with wounds infected with Pseudomonas aeruginosa and Staphylococcus aureus. This synthetic compound also made these bacteria cell membrane more permeable – making it easier to kill these bacteria. The research was published in Biofilms and Microbiomes

Research Roundup: Fighting antibiotic resistance with maple syrup, epigenetic effects from light and diet, and HPV vaccine success

Welcome to this week’s Research Roundup. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • New research finds that phenolic extract from maple syrup may boost antibiotic action. Antibiotic resistance is on the rise, with at least 2 million people becoming infected with bacteria that are resistant to antibiotics each year. Producing antibiotics to fight these “superbugs” is proving to be extremely difficult with the first new antibiotic being discovered in thirty years occurring in 2016. Researchers, learning of the anti-cancer properties of maple syrup, decided to investigate its antimicrobial properties. By mixing the syrup’s phenolic compounds — which gives syrup its characteristic golden color with the antibiotics ciprofloxacin and carbenicillin, they found the same antimicrobial effect with less than 90 percent of the antibiotic. They then tested the extract in fruit flies and moth larvae and found a similar effect. Further experiments are now planned in mice and the researchers are hopeful that one day this extract will be turned into a widely available, plant-based medicine.
  • Parental exposure to dim light at night may lead to a decreased immune response in offspring — Researchers at the Ohio State University exposed male and female adult hamsters to either a standard light/dark cycle or one with dim light at night for nine weeks. Offspring with parent(s) that experienced dim light exposure had an impaired immune response and decreased endocrine activity compared to offspring from standard light exposure parents. What is most interesting is that these epigenetic effects were transferred from the sperm and/or egg, and they were independent of light exposure in utero. The study suggests further research into light exposure at night from sources such as tablets, phones, and TVs should be done in humans.
  • A new study using mice finds that paternal diet affects offspring cognitive ability. Increasing evidence suggests that offspring development is not only impacted my maternal factors, such as the mother’s diet, but also by factors that the father has been exposed to. Epigenetic modification of germline cells has been implicated as one major causal pathway for the transmission of such changes to the offspring. In the present study, one group of male mice were fed a diet containing nutrients required for methyl group metabolism — methionine, folic acid, vitamin B12, choline, betaine and zinc, while another group was fed a standard diet of lab chow. After six weeks on the respective diets, the male mice were mated with female mice, and the offspring tested on a series of learning and memory tasks. The offspring of the male mice fed with methyl donors performed less well in all learning and memory tests. Related changes were also observed with poor activity in the hippocampus (associated with learning and memory) and downregulation of a gene associated with neuroplasticity. The study has implications for countries such as the USA, where dietary supplementation is prevalent.
animal testing, animal research, vivisection, animal experiment

Research mouse being held

  • A new function for the cerebellum has been found — the encoding of expectation of reward. The cerebellum accounts for approximately 10% of the brain volume, but contains more than 50% of its neurons. The cerebellum is often thought to function outside the realm of consciousness, being primarily involved in motor function and processing sensory input. The present study used genetically modified mice that expressed a green fluorescent protein (GFP) and photon microscopy. Scientists trained mice to push a lever to obtain a sugared reward. They found that one set of cells in the cerebellum fired when the mice pushed the lever (motor response), another set fired when the mice were waiting for the reward to arrive (cognitive response in regard to expected event) and third group fired when the reward was removed entirely (cognitive response in regard to unexpected event). This study challenges the current way of thinking about the role of the cerebellum and highlights how more research is needed to further understand how structures within the brain function in an interconnected way.
  • Discovery of a gene related to congenital blindness in zebrafish may lead to a cure for similar disease in humans. One type of congenital blindness is termed Leber Congenital Amaurosis (LBA), and leads to deformed or absent rods and cones in the eyes of children — resulting in blindness. While researching blindness in zebrafish, scientist have manipulated genes associated with rods and cones, and discovered a mutant. These genetically mutated zebrafish also have degenerated cones in their eyes, similar to humans with LBA, but the rods are not affected. Future research investigating the molecular and cellular mechanisms of rod and cone development using this new animal model may lead to a possible cure in humans.

  • In the news, we sometimes hear stories about miracle drugs being created to save loved ones from debilitating diseases. Sometimes these drugs work, in part because of some previous validation in pre-clinical work using non-human animals. Other times, they result in devastating effects because they have not gone through appropriate safety trials. It is important that our readers and the public in general understand why clinical safety trials are important and have a proper understanding of the associated risks if they are not conducted.
  • Vrije Universiteit Brussel (VUB) has restarted animal experiments at its lab in Brussels. Work was temporarily suspended late last year after an undercover video was made by the animal rights group GAIA. The institution began both internal and external audits to assess its own processes, and they have taken various measures to further improve animal wellbeing, administration, and infrastructure – with a further €13.8m earmarked for a new animal facility in the future. The decision to restart means that 27 approved projects that were on hold can now begin.
  • The human papillomavirus (HPV) vaccine, provided free to girls in Scotland aged 12-13 years old has resulted in a 90% reduction in levels of the virus. HPV is believed to account for around 90% of cervical cancer cases. The HPV vaccine owes much of its development and subsequent efficacy testing to animal models, including rabbits (Shope papillomavirus), cows (Bovine papillomavirus) and dogs (Canine oral papilloma virus). It is forecast that the HPV vaccine will lead to a 90% drop in cervical cancer cases in Scotland.

Jeremy Bailoo and Justin Varholick

Research Roundup: Red blood cell production in the lungs, sea urchin spines to fix bones, and trying to reverse aging in mice

Welcome to our fourth weekly roundup (now called “Research Roundup”). These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • new study finds that most of our blood cells are made in the lungs, not bone marrow. Using genetically modified mice that expressed a green fluorescent protein (GFP) and photon microscopy, scientists were able to track blood platelets as they circulated around the body in real time. Surprisingly, they found a large population of megakaryocytes, responsible for the production of blood cells, in the lungs. This population of megakaryocytes was found to produce upwards of 10 million platelets per hour — at least half of the body’s total platelet production. Further experiments, found another population of megakaryocytes just outside the lung tissue — about 1 million per lung. Additionally, using mice with no stem cells in the bone marrow (eliminating blood cell production there), they found that cells from the lungs migrated to and facilitated blood cell production in the bone marrow. Because of technological advances in genetic engineering and microscopy, this study challenged a decades-old assumption, central to the field of biology and medicine. This study will of course need to be replicated and assessment performed of whether these findings generalize to humans.

  • Sea urchin spines can be used to fix bones, offering a much needed refinement to the second most performed transplant procedure, after blood. Current procedures involving transplants for bone defects lead to subsequent complications as, for example, when brittle synthetic compounds break, causing further inflammation. This study therefore investigated whether the rigid structure of sea urchin spines represent a superior alternative material to currently used products. Sea urchin spines were first soaked in sodium hypochlorite for 30 min, and then rinsed in deionized water at 200C for 2 days in order to remove organic material, converting the spine to magnesium-substituted tricalcium phosphate (β-TCMP) scaffolds, while maintaining the rigidity of the original open-cell structures. When testing the material on rabbits and beagles, they found that bone cells and nutrients could flow through the pores and promote bone formation. They also found that the scaffold degraded easily as it was replaced by the new growth.

Image Credit: Lei Cao et al

  • A new study found that a population of neurons in the striatum is implicated in the Pavlovian associative learning. Pavlovian conditioning is a cornerstone of Behavioral Psychology; although the implications for subsequent research investigating links to disorders such as addiction, compulsive behavior, and schizophrenia are probably understated. In the present study, researchers exposed mice to an odor — banana or lemon — followed by a reward of condensed milk. By repeatedly pairing the odor with the reward, mice learned that a certain odor predicted a particular reward. Similar to Pavlov’s earlier experiment, the anticipation of the reward upon presentation of odor also occurred — mice licked the air — analogous perhaps to how humans lick their lips in anticipation of, for example, ice-cream. To understand how the brain regulates this response, these researchers focused on the striatum as this area has previously been associated with reward and decision making. Using optogenetics and chemogenetics, the researchers “turned-off” a tiny group of cells that support the principal neurons in the striatum. Predictably, mice with these cells turned-off only licked the air in anticipation of milk only half as often compared to baseline levels. This difference was most pronounced in mice that were first learning the odour-reward pairing and less pronounced in mice that had learned the pairing — suggesting that these cells are involved in the encoding of the Pavlovian response. This research may have further implications for other disorders as dysfunction of this group of neurons is also implicated in Huntington’s disease, Parkinson’s disease, and Tourette’s syndrome.

  • Researchers target senescent cells, cells involved in aging, to reverse the signs of aging in mice. “This is the first time that somebody has shown that you can get rid of senescent cells without having any obvious side effects.” says cell and molecular biologist Francis Rodier of the University of Montreal in Canada. Dr. Rodier was not connected to the study.  The cells also share some properties with cancer cells.  Researchers hope to explore applications that could lead to treatments for cancer as well as age-related diseases.

The mice needed for the study are genetically predisposed to faster aging allowing researchers to evaluate their new molecule. Here we see old mice which are less active and have hair loss. Humane endpoints are especially important in these types of studies.to ensure animals do not experience unnecessary discomfort. Image Credit: Peter de Keizer

  • New drug found to alleviate symptoms associated with Type 2 diabetes (insulin resistance) in mice. Diabetes affects 29.1 million Americans (9.3% of the population) with 1.4 million new diagnoses annually. It is the 7th leading cause of death in the USA and 90% of all cases of diabetes are of the Type 2 Management of Type 2 diabetes usually involves diet management and exercise, although oral medications may be used to bring glucose levels under control. Therefore, treatments that permit an individual to gain control of their life or to limit the symptoms associated with this disease are wanting. In the present study, scientists investigated the role of low-molecular-weight protein tyrosine phosphatase (LMPTP), in vivo for the first time. Using genetically modified mice that lacked LMPTP in the whole body and specifically in the liver, they found that LMPTP is associated with the development of Type 2 diabetes — improved glucose tolerance and reduced fasting insulin levels. They next developed, in vitro, a molecule inhibitor which preferentially binds to the receptor for LMPTP — blocking its action in the body. Testing this molecule, in mice, they again similar results to the experiment where the gene for LMPTP was removed (knocked out) — improved glucose tolerance and decreased fasting insulin levels. This study provided the first evidence of the signaling role of LMPTP in regards to Type 2 diabetes — and with subsequent replication and further testing may signal new hope for the millions of individuals that suffer from Type 2 diabetes.
  • The University of Cambridge has produced a series of videos about how its researchers are using animals (and people) to treat OCD – a neuropsychiatric disorder that can have debilitating effects. The three part series tracks science journalist and OCD-sufferer, David Adam, as he goes into the research labs at Cambridge and speaks to experts working with rats, monkeys and people. The video shows animal experiments being conducted, explaining why they are necessary. This is a great example of openness by the University of Cambridge. See other examples of videos being produced by labs.

Jeremy Bailoo

Research Roundup: Ending the vaccine-autism myth, spider venom for stroke victims, and causes of polycystic ovary syndrome

Welcome to our third weekly roundups. These Friday posts aim to inform our readers about the many stories that relate to animal research each week. Do you have an animal research story we should include in next week’s Research Roundup? You can send it to us via our Facebook page or through the contact form on the website.

  • Studies on the relation between the environment and autism are starting to build, ending the vaccine-autism myth started in 1998. No vaccination has met the criteria of being a cause of autism – although some environmental factors increase the risk two to four times. Our understanding of many of these risk factors has been greatly increased with the help of animal research. For example, mouse research on the relation between maternal immune activation and autism-like phenotypes was later found to be consistent in human populations. Also, links to prenatal exposure to medications with teratogens were investigated in rats and found to be consistent with humans.
  • Spiders venom saves stroke victims: Funnel-web spiders are among the world’s deadliest spiders, but their venom can be life-saving. Since the venom targets the prey’s nervous system, researchers tested whether it could be harnessed to reverse brain damage after a stroke. After traveling to Fraser Island to collect three Darling Downs funnel-web spiders, researchers at University of Queensland and Monash University “milked” the spiders to collect their venom, then isolated a protein called Hi1a — a molecule that closely resembles another known for its protective effect on neurons. The team then synthesized their own version of Hi1a and gave the compound to rats two hours after an induced stroke. Neuron damage was reduced by 80 percent. Eight hours after a stroke, it was still effective in restoring neurological and motor functions by almost 65 percent. The researchers hope to commence human clinical trials in the next few years, pending replication of these initial findings and further research into the molecule.

  • A new study has found that polycystic ovary syndrome (PCOS) may start in the brain, not the ovaries, contrary to previous belief. While the cause of PCOS is unknown, one feature of this syndrome is high levels of androgens. Using a high dose of androgens, PCOS was induced in genetically engineered mice which display a receptor for androgens in specific parts of the body (brain, ovaries, nowhere in the body and a normal control group). Mice with androgen receptors in the normal control group developed PCOS as expected, while those without receptors in the brain and in the entire body did not. Interestingly, mice without androgen receptors in the ovaries also developed PCOS albeit at a lower rate than the control group. These data replicate the finding that high levels of androgens are implicated in the development of PCOS. More importantly, they highlight that it may be the interaction of these androgen in the brain rather than the ovaries that lead to the development of PCOS. PCOS affects 5-10% of women aged 18 to 44 and this study, using mice, has provided valuable insight into the onset of this syndrome.

  • A new study finds in mice that whole body vibration (WBV), a less intensive form of regular exercise, mimics the benefits derived from regular exercise. To investigate the benefits of WBV, scientists exposed normal mice and mice which don’t produce a receptor for leptin (a hormone associated with the feeling of being full after eating) to no exercise, either daily treadmill exercise, or WBV for three months. They found that in the normal mice and the leptin-deficient mice, WBV and exercise, affected mice in a similar way — reduced body weight, enhanced muscle mass, and insulin sensitivity compared to mice that were sedentary (no exercise group). This research, using mice, suggests that WBV may be useful as a supplemental therapy for individuals suffering from metabolic disorders or morbid obesity and where regular exercise is not an option.
  • Researchers have created a backpack-sized artificial lung that was able to fully oxygenate the blood of sheep for six hours. William Federspiel, at the University of Pittsburgh, has subsequently said the device has been used successfully on sheep for five days. The device had to combine a pump and gas exchange while remaining small enough to be carried. Even smaller devices have been developed to work on rats, using ultrathin tubing, just 20 micrometers in diameter. Such technologies could allow people with lung failure to continue with many of their daily activities, rather than becoming bed-ridden and attached to today’s artificial lung machines.

Image Credit: William Federspiel

  • A study funded by the NC3Rs explores how different handling methods affected behavior in cognitive tasks. Tail handling is still one of the more common methods of handling mice in the laboratory despite variable evidence that alternative methods such as cupped or tunnel handling may be less stressful for the animal. The researchers compared how mice reacted to new stimuli after being transferred into the testing area via a tunnel or being picked up by the tail. Because being picked up by the tail may be stressful for mice, tests which involve exploration may be affected by tail handling – as one consequence of stress in mice is freezing behavior (staying immobile). They found that the tunnel handling facilitated greater exploratory behavior, indicating that the simple process of tail handling may confound behavioral measures relating to anxiety. 3Rs research like this can help to understand the needs of animals in research labs, with the aim of improving animal welfare and the replicability of experimental results.

Image Credit: Jane Hurst, University of Liverpool.

Speaking of Research

Tail or Tunnel: Handling Methods Influence Mouse Behavior in Cognitive Tasks

  • A study funded by the NC3Rs explored how handling methods influenced mice’s behavior during cognitive tasks
  • Mice were either picked up by the tail or guided into a tunnel, then transferred to the testing arena
  • Mice that were transferred in the tunnel were far more exploratory during the cognitive task
  • Acclimation to handling procedures is important

A new study published today in Scientific Reports shows that the way experimenters pick up mice can affect their behavior during cognitive tasks. The study was funded by the NC3Rs, which is dedicated to replacing, refining, and reducing the use of animals in research and testing. This particular study focused on refinement: identifying optimal handling methods for mice has important implications for both the welfare of the animals and the validity and usability of data that are collected, which could potentially lead to a reduction in the need for animals in future studies.

Image Credit: Jane Hurst, University of Liverpool.

Drs. Kelly Gouveia and Jane Hurst first placed laboratory mice near a new, attractive stimulus – urine from a novel mouse of the opposite sex – that is known to stimulate approach and investigation. The mice were allowed three sessions to grow accustomed to the new scent. Throughout all three sessions, mice were either picked up by the tail (standard laboratory practice, though there is no obvious scientific reasoning for this method) or were guided into a clear tunnel that is both affordable and easily sterilized. (The method is also easy to learn.) Mice were then carried to the test arena either by the tail or in the tunnel and allowed to explore. Gouveia and Hurst report that mice picked up by the tail showed very little willingness to explore the test arena, and therefore investigate the new stimulus, whereas those transported in the tunnel showed much higher exploration and a strong interest in the new scent.

Importantly, Gouveia and Hurst then tested the mice’s ability to discriminate between the (formerly) new scent and a second, different urine stimulus. They report that since the mice picked up by the tail performed so poorly from the start, they did not discriminate between the two scents. However, those transported in the tunnel showed robust and reliable discrimination. These findings are noteworthy not only with respect to the psychological welfare of the animals, but also for the important effects that handling and habituation have on yielding usable, reliable data. With the potential to reduce the stress associated with handling, the tunnel method could reduce the anxiety that mice display upon tail handling – thereby resulting in more species-typical behaviors, such as exploration of a novel, conspecific scent. It could also reduce the uncontrolled variation that exists in animal studies and could ultimately produce more reliable data. Thus, identifying optimal handling techniques has the potential to reduce the number of animals needed in laboratory studies in addition to refining the techniques used to study them and enhance their welfare.

Image Credit: Jane Hurst, University of Liverpool.

It is worth noting that a study by Novak and colleagues (2015) found no difference in cognitive performance between mice that were handled by the tail or by a less invasive method (“cupping” in the experimenter’s hands). Why might no difference have been found in this study? One possibility is that the cognitive task the researchers used was different from the present study (a radial arm maze vs. novel scent), and the arm maze may probe for different behaviors than a novel odor task. Another possibility is that perhaps mice “prefer” the tunnel to both tail handling and cupping, but neither the 2015 nor the present study compared all three methods. Hurst and her colleague Rebecca West did compare all three methods in a 2010 study, however, and found that mice preferred both the tunnel and cupping method to tail handling (as assessed by voluntary interaction time with the experimenter); although the cupping method produced more variable results depending on strain and sex. However, in the Novak study, mice were handled daily for many weeks, whereas in the Hurst & West study they were handled only for nine days. Of course, the most parsimonious explanation is that in every handling study, experimenter interaction is confounded with handling. That is, are the mice acclimating to the experimenters, to the handling procedures, or both?

These questions underscore the need for replication before firm conclusions about optimal handling techniques can be drawn. Nevertheless, the findings published today in Scientific Reports are an important addition to the field of animal welfare, and they emphasize the importance of constant, rigorous studies surrounding welfare issues.

Amanda Dettmer

References:

Gouveia K, Hurst JL (2017) Optimising reliability of mouse performance in behavioural testing: the major role of non-aversive handling. Scientific Reports 7: 44999. doi: 10.1038/srep44999

Hurst JL, West RS (2010) Taming anxiety in laboratory mice. Nature Methods. Oct;7(10): 825-6

Novak J, Bailoo JD, Melotti L, Rommen J, Würbel H (2015) An Exploration Based Cognitive Bias Test for Mice: Effects of Handling Method and Stereotypic Behaviour. PLoS ONE 10(7): e0130718. doi:10.1371/journal.pone.0130718

SYR: The case for using large animal models to study reproduction

michelle-bedenbaughThis guest post is written by Michelle Bedenbaugh, a Ph.D. student in the Physiology and Pharmacology Department at West Virginia University. It is part of our Speaking of Your Research series of posts where scientists discuss their own research. Michelle’s research involves examining the brain’s role in the initiation of puberty.  In this post, Michelle discusses the benefits of using large animal models to study reproduction.  If you would be willing to write a guest article for Speaking of Research, please contact us here.

With the increasing pressure to publish papers and the decreasing amount of funds made available to conduct experiments, it has become more difficult for researchers to survive and thrive in an academic setting (see here, here, and here). Scientists have had to adapt, and in many situations, this has led to a significant amount of research that relies heavily on small animal models, including rodents and invertebrates.  In addition to being less expensive than large animal models (sheep, pigs, cows, horses, etc.) there are also more genetic tools and techniques available to use in small animal models.  For example, transgenic mice, where certain genes can be either deleted or overexpressed, are used commonly by researchers worldwide.  Other cutting edge techniques, like optogenetics, where light can be used to control the activity of cells in the brain, are also being used on a more routine basis in rodent models and currently don’t exist in large animal models.

Optogenetics involved using light to control genetically modified cells inside the body

Optogenetics involved using light to turn off or on cells in the brain

While it is most likely easier, cheaper, and faster to conduct experiments using small animal models, in certain situations they are not always the most comparable to humans.  When modeling certain diseases or understanding certain physiological processes, larger animals, like sheep, pigs, and cows, provide a better model for scientists.  This post aims to look at some areas where larger mammals can provide important knowledge or understanding.

A few of the more obvious benefits to using large animal models when compared to small animal models are that large animals are more analogous to humans in regards to body size, organ size, and lifespan.  In addition to these similarities, animals like sheep, cows, and pigs are much less inbred when compared to rodents.  Some would argue that it is advantageous to use animals that are highly inbred because this decreases the amount of variability in an experiment.  However, each human has a unique genetic makeup, and sometimes solutions for problems in inbred rodents cannot be translated for use in humans.  Therefore, in these instances, it is probably more beneficial to use a less inbred large animal model.  Most large animal models also have the added benefit of being an economically important species.  The majority of researchers who use large animal models are attempting to find solutions to health issues that are present in humans.  However, successful experiments in large animal models have the ability to affect both human and animal health.  For example, if a researcher made an important discovery about the way food intake is controlled in cows, it would have the possibility of improving human health, as well as increasing profitability for cattle producers.  Because cows are very similar to sheep, it may also benefit sheep production as well.  Rodents are not an economically important species that provides food, fiber, or other essential products used by the human population.  Consequently, discoveries made in rodents and other small animal models may only benefit humans if the results are translatable.

My particular research focuses on furthering our understanding of how puberty is initiated in girls, and we use sheep as our animal model.  I won’t get into the specific benefits of using sheep to conduct puberty research today because I will discuss this more in my next post.  However, I did want to touch briefly on some of the advantages of using large animals to perform research used to study reproduction in a broader sense.

The brain plays an essential role in controlling reproductive processes.  The brain structure of large animals is more closely related to humans than small animals because large species have a sulcated cortex (meaning the surface of the brain is wrinkly) as opposed to small animal species which have a smooth cortex.

Comparison between mouse (smooth cortex) and human (sulcated cortex) brain. [Credit: Elizabeth Atkinson, Washington University in St. Louis]

Comparison between mouse (smooth cortex) and human (sulcated cortex) brain. [Credit: Elizabeth Atkinson, Washington University in St. Louis]

Sheep also have the advantage of their brain and the cellular pathways present within it being similarly organized to what is observed in non-human primates.  Hormones serve a major role in relaying information from the brain to reproductive organs and vice versa.  The actions of several hormones that aid in controlling reproduction in female sheep (like estrogen and progesterone) parallel the actions of these hormones in humans.  Older sheep also have a similar response to estrogen replacement therapy when compared to post-menopausal women.  The development and function of several structures on the ovary of sheep is also similar to that which is observed in women.  These structures have a major influence on the reproductive cycle and are critical for the maturation of female gametes (sometimes referred to as eggs).  Assisted reproductive technologies, many of which are used for in vitro fertilization (IVF) protocols in women who are having trouble conceiving, have been adapted from procedures used in livestock species.  For example, artificial insemination, where semen is collected from a male and usually frozen so that it can be used to inseminate a female at a later time, is commonly used in cows, sheep, horses and pigs and is similar to procedures conducted in humans.

Credit: Livestock Breeding Services - http://www.livestockbreedingservices.com.au/images/servicesai.jpg

A laparoscopic procedure is used to artificially inseminate sheep

 

Embryo transfer, where embryos from one female are placed into the uterus of another female, are also used in livestock species and humans.  In addition, sheep are also an excellent animal model for studying pregnancy.  Sheep are used often to examine how stress, maternal nutrition, and exposure to excess hormones or toxins affect the development of a fetus.

These are just a few examples that display reproductive processes occurring in many large animal species are easily relatable to those same processes which also occur in humans.  I only touched on a few species today, but there are many more animal models that are underused in research and would serve as great models for humans.  In addition, I only discussed some of the ways these animals can be used to study reproduction when in fact they can be used to mimic many other biological processes that occur in humans.  Depending on the subject matter being researched, the use of some animal models is more appropriate than others.  Regardless of cost or time, researchers should always consider which animal model may be the most appropriate for their experiments.  I believe conducting research in a variety of species as opposed to just one or two species will always be more advantageous and will aid us in solving health issues in humans more quickly.

Michelle Bedenbaugh