Mice stressed in simulated weightlessness show organ atrophySeptember 04, 2007Rutgers researchers track osteopontin-dependent changes in thymus and spleen New Brunswick, N.J. - A ground-based, experimental model used to simulate astronaut weightlessness in space has provided Rutgers scientists an opportunity to study the effects of stress on immune organs. Earlier collaborative research with Japanese scientists employing this model implicated the protein osteopontin (OPN) in bone mineral loss associated with simulated weightlessness in mice. This research was made possible by the creation at Rutgers of a mouse unable to make OPN (a "knock-out" mouse). Studies with this Rutgers mouse have demonstrated that OPN likely plays a role in a variety of human problems including cancer metastasis, multiple sclerosis and other autoimmune diseases, osteoporosis and certain inflammatory responses.
The new study, which also simulated weightlessness, demonstrated that OPN is required for the atrophy of immune organs brought on by the stress resulting from hindlimb unloading - a technique employed to simulate weightless conditions by lifting the animal's body weight off its hind legs. Results are presented Sept. 3 online in the Proceedings of the National Academy of Sciences (PNAS) and in the Sept. 11 print issue. "The bone loss seen in astronauts or bedridden patients is not a stress issue," explained David Denhardt, a professor in the Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey. "They are experiencing a loss of weight bearing on the bones, and the loss of bone mineral is a direct result of this load reduction." The presence of OPN, a feature common to both the bone loss and the organ atrophy, is produced by two different causes - weightlessness and stress - coincidentally related to the same laboratory conditions. OPN is the continuing focus of Denhardt's research interests. His long-term goal is to develop an OPN antibody - a monoclonal or target-specific antibody - that will inhibit OPN function in lab mice, and ultimately, in humans. This antibody could prove useful in treating the many destructive diseases associated with OPN. Denhardt's graduate student Kathryn Wang, a co-author on the PNAS paper, had previously conducted experiments in which the mouse was positioned in such a way as to produce hind limb unloading. This simulated weightless condition produced OPN-dependent bone loss in the hind limbs and provided a potential testing ground for possible OPN antibodies. The specialized equipment for that experiment was supplied by another co-author on the paper, Yufang Shi, a professor in the Department of Molecular Genetics, Microbiology and Immunology at Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey. Shi, an authority on stress, suggested that along with the bone loss studies, the Rutgers researchers should look at the spleen and thymus - the organs responsible for most of the animal's immune cells. If stress affects the spleen and thymus so that they atrophy, the immune system becomes impaired. People under severe stress often get sick. The Rutgers scientists took their colleague's advice and compared the OPN-deficient knock-out mice to normal mice, with some dramatic results. "To our astonishment and surprise, the OPN-deficient animals responded differently to the stress than the normal controls," Denhardt said. "We had no basis to expect this, but the spleen and thymus of the OPN-deficient animals remained normal whereas there was atrophy of the spleen and thymus in the normal controls. This was a novel and totally unexpected result for which we have no explanation at this time. The next phase of our research will ask what exactly is going on." The stressed normal mice also displayed elevated levels of corticosterone - a hormone known to induce apoptosis (programmed cell death), a process evident in the spleen and thymus of these mice and a possible mechanism underlying the atrophy. Denhardt said that their results indicate that OPN needs to be present for these stress related symptoms to occur, pointing to a whole new physiological realm in which the culprit osteopontin is causing problems. Rutgers, the State University of New Jersey | |||||||||||||||||||||
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Related Atrophy Current Events and Atrophy News Articles MU logo News Bureau University of Missouri About the News Bureau Contact Us Home / News Releases / 2009 MU Researchers Discover Target that Could Ease Spinal Muscular Atrophy Symptoms There is no cure for spinal muscular atrophy (SMA), a genetic disorder that causes the weakening of muscles and is the leading genetic cause of infant death, but University of Missouri researchers have discovered a new therapeutic target that improves deteriorating skeletal muscle tissue caused by SMA. The new therapy enhanced muscle strength, improved gross motor skills and increased the lifespan in a SMA model. The prevalence of gluten-sensitive enteropathy in iron-deficient anemia patients Gluten sensitive enteropathy (GSE) is an autoimmune enteropathy due to food gluten intolerance in genetically predisposed people. Patient-derived induced stem cells retain disease traits hen neurons started dying in Clive Svendsen's lab dishes, he couldn't have been more pleased. The dying cells - the same type lost in patients with the devastating neurological disease spinal muscular atrophy - confirmed that the University of Wisconsin-Madison stem cell biologist had recreated the hallmarks of a genetic disorder in the lab, using stem cells derived from a patient. Molecular Therapy for Spinal Muscular Atrophy Closer to Clinical Use Spinal muscular atrophy, a neurodegenerative disorder that causes the weakening of muscles, is the leading cause of infant death and occurs in 1 in 6,000 live births. Genetic test for spinal muscular atrophy should be offered to all couples, says the ACMG Carrier screening for spinal muscular atrophy (SMA)-a serious genetic disease affecting approximately 1 in 10,000 infants that causes progressive muscle weakness and death-should be made available to all families, according to a new practice guideline issued by the American College of Medical Genetics (ACMG). Rhode Island Hospital study finds link between obesity, type 2 diabetes and neurodegeneration New research from Rhode Island Hospital found that obesity and Type 2 Diabetes Mellitus (T2DM) can contribute to mild neurodegeneration with features common with Alzheimer's disease (AD) - the first study to show that obesity can cause neurodegeneration. Cognitive problems associated with diabetes duration and severity Individuals with mild cognitive impairment appear more likely to have earlier onset, longer duration and greater severity of diabetes, according to a report in the August issue of Archives of Neurology, one of the JAMA/Archives journals. Identification of protein able to stimulate production of T-cells A team of Canadian and Finnish scientists has identified a protein able to stimulate the production of T-cells, the white blood cells involved in the recognition and the elimination of infectious agents. Automated MRI technique assists in earlier Alzheimer's diagnosis An automated system for measuring brain tissue with magnetic resonance imaging (MRI) can help physicians more accurately diagnose Alzheimer's disease at an earlier stage according to a new study published in the July issue of the journal Radiology. Penn researchers gain new insights on spinal muscular atrophy Researchers from the University of Pennsylvania School of Medicine discovered that the effect of a protein deficiency, which is the basis of the neuromuscular disease spinal muscular atrophy (SMA), is not restricted to motor nerve cells, suggesting that SMA is a more general disorder. More Atrophy Current Events and Atrophy News Articles |
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