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Better housing fights cancer in mice

Enriching animals' environments does much more than improve their psyches -- it may fight deadly disease, according to a study published online today (July 8) in Cell. Example of enriched environmentImage: Adam MartinLiving in larger spaces with access to more toys and companions helped shrink, or even eliminate, tumors in cancerous mice. "The findings are very interesting and also very provocative," said physiologist linkurl:John Hall;https://lawwebn.umc.edu/cgi-local/hr/intranetEmployeeAndDe

By | July 8, 2010

Enriching animals' environments does much more than improve their psyches -- it may fight deadly disease, according to a study published online today (July 8) in Cell.
Example of enriched environment
Image: Adam Martin
Living in larger spaces with access to more toys and companions helped shrink, or even eliminate, tumors in cancerous mice. "The findings are very interesting and also very provocative," said physiologist linkurl:John Hall;https://lawwebn.umc.edu/cgi-local/hr/intranetEmployeeAndDepartmentListing/employeeListing.pl?Id=2wdFQVetKv of the University of Mississippi Medical Center, who was not involved in the research. "[An] enriched environment can reduce tumor growth, I think that's clear." The results may have important implications for cancer research, added neuroscientist linkurl:Anthony Hannan;http://www.florey.edu.au/about/management-and-staff/scientific-staff/anthony-hannan/ of the Howard Florey Institute in Melbourne, Australia, who also did not participate in the study, in an email to The Scientist. For example, "an experimental drug might show different effects in a preclinical trial, depending on whether the animals are housed with enrichment objects, or in a more sparse environment." Providing rodents with an enriched environment leads to a number of neurological changes in the brain, and can impact the progression of neurological diseases. But how the enriched environment influences cancer growth is not clear. To answer this question, neuroscientist linkurl:Matthew During;http://biomed.osu.edu/neuroscience/15145.cfm of The Ohio State University College of Medicine and his colleagues gave some mice a housing upgrade -- from standard mouse cages with 4 other mice to living areas 40 times larger, with more hiding places, more playmates (15 to 20 animals), and more toys. The team then injected enriched and normal mice with melanoma cells and monitored the progression of tumor growth. Remarkably, just two and half weeks later, mice housed in the enriched environments for 3 weeks prior to inoculation had tumors that were 43 percent smaller (by volume) than those housed in normal cages. Tumors of mice in enriched environments for 6 weeks before the injection were 77 percent smaller (by weight) than those in control mice. Furthermore, some of the mice in enriched environments had no visible tumors at all, whereas all of the control mice had solid masses. "The result was very robust and much more profound and much more exciting than we had predicted," During said. It was so shocking, the researchers repeated the experiment over the course of 5 years with some 1,500 mice to verify the results. They even demonstrated the protective effect of the enrichment in another cancer model -- colon cancer. Their results show that "sensory, cognitive and motor stimulation can protect against many diseases, and not just those involving the brain," said Hannan. Now, During said, "the question is really to find out the aspects of the environment" that are causing the tumors to shrink. The effects cannot be attributed purely to increased exercise, for example, as non-enriched mice that ran on wheels for 4 weeks prior to inoculation did not see a reduction in tumor growth. Delving into the mechanism by which the environment might be inducing its protective effects, the researchers identified several key players, including brain-derived neurotrophic factor (BDNF), the expression of which is known to be influenced by activity and environment. Overexpression of BDNF mimicked the results of the enriched environment, and knocking down BDNF blocked the effects of the enriched environment on tumor growth. Furthermore, the scientists saw a steep reduction in leptin -- a protein hormone that plays a role in regulating appetite and metabolism -- in mice in enriched environments. Knowing that leptin expression is regulated at least in part by the sympathetic nervous system, they tested the effects of a β-blocker known as propranolol, which inhibits that system, and found that it the drug completely blocked the effects of the enriched environment on tumor growth. The role of BDNF in this process makes sense, researchers agree, but other aspects of this proposed mechanism "are somewhat provocative and might be challenged in the future," Hall said. For example, β-blockers have long been used for the treatment of high blood pressure, he said. "If they actually had an effect to promote tumor growth, I think that would have been seen in humans." In addition to potential implications of this work for developing a cancer therapeutic -- which During and his team are now looking into -- there are more basic considerations about how to house laboratory animals, Hannan said. "The dramatic effects shown in this Cell paper, together with many previous papers on rodent models of brain disorders, suggest that all biomedical researchers (not just neuroscientists) need to think carefully about housing conditions and other environmental factors in their experiments." L. Cao, et al., "Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition," Cell 142: 52-64, 2010.
**__Related stories:__***linkurl:Lab Toys;http://www.the-scientist.com/article/display/56010/
[October 2009]*linkurl:No role for neurogenesis in enrichment?;http://www.the-scientist.com/news/display/23351/
[1st May 2006]*linkurl:Improving the Lives of Laboratory Animals;http://www.the-scientist.com/article/display/14638/
[26 April 2004]
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Comments

Avatar of: Ted Braun

Ted Braun

Posts: 1

July 8, 2010

The influence of architecture on our lives has been ignored. Yet we know there is a connection between what we feel and how we feel. http://qedrealestate.wordpress.com/2010/07/08/the-importance-of-touch-in-architecture/
Avatar of: john toeppen

john toeppen

Posts: 52

July 8, 2010

Getting more out of life makes it better and longer in people as well as mice. If were were to apply this understanding in a broader sense we would all be better off.
Avatar of: anonymous poster

anonymous poster

Posts: 11

July 8, 2010

This is an important and interesting study. I am not sure if this study would have got funded from any agency if it was proposed as a hypothesis based grant application. The study also shows how our life-style affects our health and what biomedical research should target. I guess this study will have a profound impact in the future.
Avatar of: Miriam Reynolds

Miriam Reynolds

Posts: 2

July 8, 2010

Stressed research animals (all research animals) make for inconsistent model systems. What is the scientific method without consistency?
Avatar of: anonymous poster

anonymous poster

Posts: 2

July 8, 2010

These results are certainly promising and seem convincing. As a animal behavior researcher I'm very pleased to see them appear in print. I also find them important insofar as they converge on other research that shows the influence of stress on tumor growth and more generally on immune function. Nevertheless, the studies reported here involved mice not humans. Let's wait until we see results from similar human studies, experimental or otherwise, before we go too far off the deep end.
Avatar of: Ellen Hunt

Ellen Hunt

Posts: 199

July 8, 2010

Our immune system is regulated by the nervous system. More active, happier people are healthier.
Avatar of: Jun Zhang

Jun Zhang

Posts: 10

July 12, 2010

Better housing, light exercise, massage, and etc may promote the blood flowing, immune cells distribution, normal cell activation... indirectly inhibiting/removing useless/harmful un-normal cells.\nAlso applicable in bone degeneration disease...like bone AR...?
Avatar of: Stan Young

Stan Young

Posts: 3

July 22, 2010

This fun result appears to be robust. Fine. The thing that is not fine is the use of rodents to predict human carcinogens. Mice and mice are very poor predictors of each other so why should they predict humans? Air flows, height of cages in rooms, etc. affect tumor spectrum. Rodent studies cost millions that could be better spent finding useful bioactive molecules.

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