How did this field of research began? An interesting observation taken from a Dispatch article, Oct, 8, 1999.
"Glaser said it was his wife, Janice Kiecolt-Glaser (see pervious page for her human studies), who convinced him more than a decade ago that the field had a future. 'I didn't believe this stuff.' he said. 'She convinced me to give it a try, and it worked.' The two published their first paper in 1984. It showed that academic stress altered medical students immunities. 'The next year we got our first grant,' Glaser said. 'And we've been funded ever since.'"
Yes they have!
In the Fall of 1999, OSU received $18 million from the National Institutes of Health to study the effects of stress and aging on how fast wounds heal. $9.9 million, from Office of Behavioral and Social Sciences, goes toward establishing the Center for Stress and Wound Healing. $8.5 million, from National Institute on Aging, will fund research into stress, aging, and wound healing. We urge you to visit the OSU site and read what the center is doing. At this time more than half of the researchers involved at the center are using animals.
We agree with Morton Frank, a retired Philadelphia physiologist, who after attending a Glaser talk in 1998 stated, "I think it's obvious and in a certain sense it doesn't need to be proven."
The center can use all the consenting adults they want, but STOP KILLING THE ANIMALS!
The Lay Abstract provides with the protocol gives the goals of this experiment.
It is funded with taxpayer dollars. Our comments are italicized.
"For years evidence has suggested that stress, such as that following the death
of a family member, or the requirements of a demanding job may lead to a higher
frequency of colds and disease. Learned via human observations and experiments
In addition, it is well appreciated that old age complicates our response to
infections. Influenza infection, which typically causes transient discomfort
in younger individuals, is one of the leading causes of morbidity and mortality
in the elderly population. Today's society is characterized by both an increasing
mean age and high stress, thus the accompanying immune alterations will potentially
affect a larger portion of the population. However, few carefully controlled
experiments have been designed and performed to identify the biological mechanisms
that underlie age and/or stress-mediated alterations in immune responsiveness.
Previous observations in our laboratories have shown that stress suppresses
the ability to fight viral infections in a manner that mimics the effect of
aging. We believe that with both advancing age and psychological stress, products
of the endocrine and nervous mediate the noted immune suppression. This
data has been gained by human experimentation and observation. Our goal
is to gain a better understanding of these products and how to modulate their
production and/or effects on the immune system. To this aim, a steroid hormone,
androstenediol, has been shown to counterbalance some of the suppressive effects
of the endocrine products on the immune system. In these experiments, we will
examine the effects of aging, stress, and androstenediol on the immune response
to influenza virus infection in young, mature, and old mice."
And the experiments in this protocol continue to grow...
Amendment approved April 5, 2002 adds the elements of 97A0015 & 00A0169 (see below) but will use 2,188 mice and now include elements of social disruption.
Amendment approved April 19, 2002 authorizes a new species, 1,080 rats, and procedures, intermittant confrontation.
Amendment approved February 11, 2003 adds an additional 90 rats who will receive an injection of a drug to block the normal stress response of the animals.
Amendment approved May 6, 2003 adds an additional 840 mice. Also a modification to SDR, paired fighting stress. The aggressor mouse will attack and defeat a single mouse.
UPDATE: June 4, 2003 - ILACUC approves an additional 630 mice to study the effects of lavender or lemon oil fragrances on the response to stress and infection.
Actually they say "the positive effects", which seems like a conclusion to me. Maybe mice don't like those smells. Hey let's get some of that Buckeye Egg Farm smell and see if the mice get stressed breathing that smell? Who knows maybe the mice would begin thinking about a long forgotten life in the fields and actually relax.
UPDATE: May 10, 2004 - ILACUC approves an additional 320 mice to assess the impact of social stress on susceptibility to bacterial pathogens (Salmonella typhimurium). An LD50 test will be conducted on the animals. John Gunn is also added as a co-investigator.
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The variation on this experiment from others is that, "These studies will allow us to study hormonal and immune changes that are induced by the lock stressor and help us to understand how stress can reactivate latent HSV (Herpes Simplex Virus)."
The lay abstract for this protocol matches 01A0039. Modified at somepoint in it's life to incorporate maternal separation.
The variation in this project: "In these experiments, we will examine the influence of a physical and a social stressor on carcinogenesis. We will monitor the mechanisms that lead to DNA damage, gene mutations and the induction of lung cancer. Hmmm, People quit smoking! Hopefully, by gaining a better understanding of the mechanisms controlling these responses, we will be able to prevent tumor initiation and development associated with chemical carcinogens."
The specific mice species are listed in this protocol as the variant in this experiment is the mice. "Selection of the specific strains of mice are based on the fact that (1) C57BL/6 mice have been used extensively in this laboratory to assess the effects of stress on the response to viral infection and (2) SKH-1 mice are hairless and will facilitate the monitoring of the epidermal regions, thus reducing the need for further manipulations, such as depilation. Wow, I bet the mouse are thrilled!
Again the same setup for the experiment with the variant being: "Hopefully, by gaining a better understanding of the mechanism controlling the immune response, we will be able to manipulate the ability of stressed and aging individuals to recover from a common clinical biopsy procedure and resist infection."
Published 10/18/01 - STRESS LEADS TO INFECTION IN SKIN WOUNDS, STUDY SUGGESTS
Amendment Update December 18, 2003
To keep those rolling in, ILACUC approved the use of 80 additional mice and
procedures for a pilot study to measure oxygen delivery to injured tissue. In
the request the PI states: "We have established the fact that stress impairs
wound healing." And so did your colleagues who had already established
the fact by using human volunteers!
Early trauma, neglect, loss of a parent or inadequant parenting are stressors that confront some children. Many studies have shown that inadequate parenting, especially during the neonatal period may result in long lasting effects on behavior and physiology. ...Our goal is to gain a better undrestanding of the effects of early stress on immune activity. In these experiments, rat pups (newborns to 5 months) will be separated from the dam for several short periods of time. The effects of stress on the immune response of these pups will be tested later in life using various challenges ( biopsy, bleeding, restraint stress, induction of inflammation) later in life. This information will be useful in studying possible interventions in people that have experienced trauma during early childhood."
Social Disruption will be as a social stressor. SDR results in increased fighting and may potentially lead to physical wounds in 5% of the animals.
from the Lay Abstract: "Exposure to ultraviolet radiation can cause the development of skin cancer. The goal is understand how common behavioral stressors may alter our immune responses and thus alter the growth and progression of skin cancer."
A variety of the experiments have been modified to perform one of the four procedures on a mouse.
"Social stress elevates serum nerve growth factor (NGF), which is known to act on cells of the immune system.
According to the literature, the source of the stress-induced NGF is the salivary glands."
"The blood vessels and salivary ducts of the glands will be ligated with suture and the glands will be removed."
"To determine if stress-induced increases in glucocorticiods are important, the adrenal glands will be removed."
"The spleen is innervated by sympathetic nerve fibers which release catecholamines, such as noradrenaline, into the tissue during stress. To ascertain the contribution of this nerve in the splenic response to stress we will perform an axotomy." ..."The splenic nerve will be carefully dissected from the vessels and cut prior to entering the splenic capsule."
"The changes in the spleen following social stress may be involved in the altered inflammatory responses and leukocyte trafficking patterns which have been observed in stress influenza-infected mice. To investigate this possibility, the spleen will be removed."
Mice are placed in 50ml centrifuge tubes (with many holes) for 2-3 cycles prior to biopsy/infection and followed by 5-7 subsequent cycles. Mice are placed in tubes at 6:00PM(lights out) or at 9:00PM and removed at 9:00AM (lights on at 6:00AM). Control mice are food and water deprived during the same time period. These mice are free to roam in their cages.
In rodents, aggressive behaviors take three basic forms: offensive, defensive, and submissive. These behaviors are useful in establishing and maintaining social hierarchies in organized groups of animals. After a 2 week acclimation period, "aggressor" mice are identified in each cage by using behavioral observations. The aggressor mice are switched between cages at the beginning of the 12-hour dark cycle.
Modified SRO, developed to achieve similar goals, while restricting the duration of aggressive behavior and injuries. To disturb the social order in the home cage of mice, an aggressive intruder will be introduced into a cage of 3-5 residents. Intruders will be singly housed male mice selected on the basis of pre-experimental screening for aggressive behavior. Screening will include placing the intruder into a home cage of another mouse. Only intruders that initiate attacks within 5 minutes and show consistent aggressive attacks towards the resident will be used.
During SDR, the aggressor is expected to start attacking the cage residents within 5-10 min. If one or more of the residents should attack the intruder, it will be replaced with a new intruder. All SDR cycles will begin at 5 PM and will last 2 hours. Mice will undergo 6 SDR cycles over a week: 3 nightly cycles, one night off, and 3 more cycles. The subjects in these experiments will be the defeated residents and not the intruders.
To read observations by the OSU Veterinary Staff of a SDR session click
Vet Observation Page 1.
Vet Observation Page 2
What else happens to these mice? The following information is taken from Animal Observations.
Read a short story about Chris the mouse.
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SOCIAL STRESS BOOSTS IMMUNE SYSTEM'S FLU-FIGHTING ABILITIES
