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Mice permitted to reside in a setting resembling the wild showed diverse conduct in comparison to laboratory mice kept in enclosures, as shown in a fresh study.(Image credit: Matthew Zipple)ShareShare by:
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The internet suggestion to “go outside” to improve your mood might be supported by research — at least regarding lab mice.
A current piece of research reveals that mice living in natural surroundings are not as uneasy as those dwelling in secure, box-shaped cages. This could emphasize a crucial deficiency in laboratory investigations, including those assessing the wellbeing and efficiency of medications ultimately aimed at humans.
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“What accounts for the large disparity in outcomes between animal models utilized in labs and practical results observed when assessing [numerous] drugs in humans?” stated Matthew Zipple, the primary researcher for this study and a postdoctoral fellow at Cornell University. “A significant portion of this effect might be attributed to the exceedingly contrived, regulated setting where laboratory animals are housed.”
The findings were detailed this past December in the periodical Current Biology.
Less anxious in the outdoors
Both wild mice and humans enjoy multifaceted social environments, with wild mice continuously moving, hunting for sustenance, digging, and confronting hazards, notably the numerous predators preying on them.
Conversely, lab mice remain in confined cages together with a couple of same-sex siblings. In such environments, food and hydration are consistently accessible. Examining medications on these mice might resemble restricting studies to prisoners in individual detention, as per Zipple’s remarks to Live Science.
Zipple, in cooperation with his team, aimed to analyze the mental state of two collections of lab mice: a group maintained within the lab and another residing outdoors with other mice in a fenced space, abundant with grass, ground, and direct view of the sky. To achieve this, they employed a typical labyrinth called the “elevated plus maze,” featuring two enclosed sections and a pair of exposed, catwalk-style arms.
Upon initial introduction to the maze illuminated by bright lab lights, lab mice generally venture into the open arms, perceive them as alarming, and essentially avoid them afterwards. Instead, they favor staying inside the comparatively safer, encased segment of the maze. Such reactions are reliable to the degree that researchers utilize the exposed arms to trigger and quantify anxiety among lab mice.
The mice authorized to wander outdoors devoted more time investigating the “open” arms of the maze.
However, Zipple’s team realized that mice existing in a naturalistic setting were not intimidated by the exposed arms at all. They allocated an equal amount of time discovering these zones during subsequent maze trials as they did initially, even in illuminated conditions.
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Concurrently, cage-dwelling mice that were relocated to live outside also showed diminishing maze anxiety; animals initially displaying evident concern around the open arms, when then exposed to a week outdoors, consequently invested twofold their time exploring the open arms compared to those that persisted living within cages.
Andrea Graham, an evolutionary ecologist from Princeton University uninvolved in the research, said the employment of the standardized maze presented a “highly potent approach to highlight the constraints of established methods.”
Caged mice have other key differences
Graham’s laboratory has verified that mice residing in lab cages exhibit immunological distinctions from mice existing outdoors, encountering soil, plants, and vast populations of different mice. She underscores the importance of this factor.
In a prominent instance from 2006, a drug referred to as TGN1412 appeared to strengthen the immune mechanism versus leukemia among lab mice, but sparked an almost fatal immune reaction in the initial six healthy human participants exposed to the substance. Further research subsequently exposed that, in the lab mice, the drug triggered immune cells accountable for moderating and alleviating the immune response. Conversely, within mice inhabiting realistic outdoor setups, the drug instead stimulated cells escalating the immune response to the degree of triggering the body to attack itself.
Mice present in realistic outdoor environments not merely act in varying manners, but similarly possess distinct immunological signatures relative to mice kept within cages.
“If we constrain our studies to encompass merely a few different genotypes [genetic compositions] of laboratory mice across homogenous immunologically unstimulating, psychologically unstimulating conditions, our capacity to explore the entire scope of the human immune or nervous system response to external stimuli remains limited,” clarified Graham to Live Science.
Implementing practical outdoor enclosures requires certain initial monetary investments coupled with effort, also curtailing the rigorous supervision applied to study organisms to alleviate confounding parameters within experiments. Consequently, these factors uproot biomedical scientists out of their comfort area, according to Zipple.
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Yet, incorporating tests featuring these less-confined mice could potentially conserve considerable endeavors and financial assets on the human trial component by pinpointing drugs bearing elevated probabilities of successful transposition from laboratory to clinical applicability, the study’s creators assert. Currently, Zipple, in collaboration with his colleagues, is examining distinctions in aging patterns between caged and outdoor-living mice.
“The overarching goal constitutes the formation of a roster encompassing biomedically pertinent actions, phenotypes [observable qualities], as well as mental characteristics exhibiting similarities between lab and field setups,” he stated, in view of easing the task of relating findings back to humans. He additionally conveys aspirations to synthesize a “roster of characteristics showing considerable deviation.”
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Stephanie PappasSocial Links NavigationLive Science Contributor
Stephanie Pappas contributes as a writer for Live Science, discussing subjects varying from geoscience to archaeology to the human brain along with behavior. She formerly served as a senior writer to Live Science, but is now a freelancer based out of Denver, Colorado; regularly contributing to Scientific American also alongside The Monitor, the American Psychological Association’s monthly publication. Stephanie secured a bachelor’s degree in psychology from the University of South Carolina and a graduate certificate in science communication from the University of California, Santa Cruz.
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