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Mice living in crowded areas get stressed

The following article describes one of many poster presentations set for this year's faculty convocation Aug. 21. This year’s theme is “Creating Collaboration” and will highlight various clinical, research and educational projects undertaken as a group effort.

by Mary Helen Yarborough
Public Relations
A study using two types of female mice has concluded that rodents living in high-density environments experience greater stress, diminished immune indicators and are less inclined to roam around and gain weight.
 
Drs. Deanne Lathers, Kathy Laber and Lynn Veatch meet in the lab. Their research study, “Effects of Housing Density on Stress, Immune Function and Behavior,” will be presented at the faculty convocation Aug. 21.

The study, “Effects of Housing Density on Stress, Immune Function and Behavior,” was funded by the Veterans Administration (VA)  and was a collaboration of MUSC and VA researchers headed by study initiator Kathy Laber, DVM, MUSC vice chair of comparative medicine; behavioral study leader Lynn Veatch, Ph.D.; stress hormone study leader Marcelo Lopez, Ph.D.; and immune study leader Deanne Lathers, Ph.D. The team worked collaboratively to develop the study design, and a grant request to fund the project was written by Lathers. All of the researchers except Lopez, a behavioral scientist for MUSC, have dual assignments from the VA and MUSC.
 
For about 10 weeks, the study involved 180 mice, half of them a stress resilient type called C57BL/6J (C57), and the other half a strain of mice that is stress sensitive called BALB/c (BALB).
 
The two sets of mice were placed into 75-square inch cages at varying densities: two mice per cage, five mice per cage and 10 mice per cage. Mice had constant access to food and water, and the ventilated cages were changed out every other week, which is standard.
 
Researchers studied indicators, including the stress hormone corticosterone, physiology such as weight gain; behavior, such as whether the animal’s movement was hesitant or exploratory; and the immune system, which was analyzed for changes in levels of so-called helper T-cells and the cytotoxic, or killer, T-cells. Helper T-cells are those that direct immune responses, while cytotoxic T-cells attack foreign or unwanted cells.
 
The study is unique because the research looked at a number of variables in the high density study, Laber said. “Previous studies have not systematically evaluated the effect of housing density and duration of housing density on behavior with in-depth analysis of immune function and stress,” she added.
 
Researchers were not surprised by most of the results that showed that a more crowded environment increases stress levels in more high-strung BALB mice, but they seemed perplexed that the more laid back C57 mice also showed increased indicators of stress.
 
“For the C57s, there was an impact at the high density population,” Laber said.
 
Unlike the BALB, the C57 gained weight, which would indicate stress resilience, but they also experienced increased levels of corticosterone levels. All four stress indicators  were altered for the BALB, including its behavior.
 
Laber said that behavior response was evaluated in two ways: how much time the mouse spent hugging the walls as through afraid to move; and how much time is spent moving about the cage.
 
“What we saw in the animal that was stress sensitive, when they were housed at 10-mice per cage, they decreased activity and didn’t want to move,” Laber said. “For the stress resilient mouse, the high density didn’t affect them.”
 
Another behavior measured was the mice’s exploratory response—how many times the mouse moved from the outside edge of the cage to the center. “The BALB froze,” Laber said. “And the C57s were less reluctant to explore. It affected their behaviors in different ways. …but both showed some level of stress behavior. …This means that both types of mice could show higher levels of stress,” Laber said.
 
Next, the researchers will break down the T-cell responses in more detail to see which may or may not have been impacted by the density response, Lathers said.
 
“We’ve covered a lot of disciplines: behavior, immune, physiology, stress hormones. And we managed to hold this case size while we modified the variables,” Laber said. “In other studies, they have changed the cage size, for example. We kept everything the same so that it was relevant.”
 
Whether the results could prove helpful in understanding stress responses in humans remains to be seen. Lathers said that it is possible that the study would consider human stress responses at a later date.
 
What is more immediately useful, however, is that the study could help researchers save a lot of research dollars by increasing the number of mice per cage.
 
Currently, the standard cage population limit is a maximum of five mice, according to the National Academy of Sciences. Research institutions must adhere to this standard to maintain accreditation. Although the cost to maintain a cage of mice is less than a dollar at MUSC/VA, the costs can add up if large numbers of mice are used. Laber said that if certain mice indicate relative comfort in a more crowded cage, then the evidence could be presented to the national academy and potentially influence the density requirements for housing mice.
 
Meanwhile, Lathers credited assistance from students and facility staff for making this study possible. “MUSC student Jennifer Mulligan and lab technician Kiki Gibbs were instrumental in the study,” Lathers said. “And thanks also to Krista Harris and her staff at the VMU that were instrumental in weighing the animals, changing the cages and checking on the status of the animals.”
 
When it is completed, the study will be submitted for publication in a professional journal.
   

Friday, July 27, 2007
Catalyst Online is published weekly, updated as needed and improved from time to time by the MUSC Office of Public Relations for the faculty, employees and students of the Medical University of South Carolina. Catalyst Online editor, Kim Draughn, can be reached at 792-4107 or by email, catalyst@musc.edu. Editorial copy can be submitted to Catalyst Online and to The Catalyst in print by fax, 792-6723, or by email to catalyst@musc.edu. To place an ad in The Catalyst hardcopy, call Island Publications at 849-1778, ext. 201.