The worst part of being sick is not always muscle aches and cough. It is the fog head, crankiness, apathy and fatigue in short, what the researchers call the behavior of the disease. A new study reveals a molecular mechanism that explains why we feel so lousy when you're under the weather.
"There is a beautiful study that covered a lot of ground," said neuroimmunologist Colm Cunningham of Trinity College in Dublin who was not connected to the research. "What does that they found is very plausible. "
Although the disease is unpleasant behavior, researchers believe that the symptoms we suffer during a viral or bacterial infection are beneficial, allowing us to turn our energy in the fight against pathogens that have invaded our body. for cancer patients and people with autoimmune diseases, however, the disease's behavior can be an undesirable side effect of treatment with immune molecules called interferons that our cells naturally release when we have an infection.
the condition posed a puzzle for researchers because they assumed the blood-brain barrier, a protective system which excludes most agents pathogens and immune molecules in the brain, could block the immune system signals. Although scientists have identified several mechanisms that allow such messages to cross the barrier behavior and influence, the issue of how the immune system and brain communicate "was only partially answered," said immunophysiologist Keith Kelley of the University of Illinois, Urbana-Champaign, who was not connected to the new study.
to immerse themselves in sickness behavior mechanisms, neuropathologist Marco Prinz of the University of Freiburg in Germany and colleagues exposed mice with a virus that causes a brief illness. The researchers assessed the effects of the pathogen using a standard test for depression in rodents in which the animals are placed in a container of water. Rodents usually struggle to get out of the water, but depressed animals quickly give up and float. Souris has spent almost twice as floating time if they were infected with the virus, suggesting that it affects their behavior.
The researchers found that the virus has stimulated mice to produce a type of interferon, interferon-β. In turn, interferon-β receptor molecules stimulated the protective membranes of the brain and the cells that line the blood vessels of the organ, part of the blood-brain barrier.
To determine whether these receptors trigger the disease behavior, Prinz and his colleagues compared normal mice with genetically modified animals that lack the receptor. After injecting the mice with RNA molecules that trigger the same immune responses as viruses, scientists have rodents with two tests to measure their mental abilities and mood. In the float test, normal mice spent about 50% more time to drift than the genetically engineered mice, the researchers report online today in Immunity , suggesting the animals are more vulnerable to depression if they have the receiver. In a learning test which requires animals to remember the location of a platform in a water tank, RNA injections did not affect the performance of mice lacking receptors. But the normal mouse performance decreased by approximately 50%. "Their cognitive abilities have been massively altered," says co-author Thomas Blank, also a neuroimmunologist at the University of Fribourg.
Prinz, Blank, and colleagues identified two parts of a mechanism that relays immune signals through the blood-brain barrier, but they still need to nail this molecule has caused changes in the brain. they found that in response to interferon-β, the blood vessel cells produce another molecule called CXCL10. the researchers then measured the electrical activity of neurons in the hippocampus, a part of the brain that helps form memories and shapes as our emotions. CXCL10 responses changed in a way that would reduce animal neuron's ability to learn. "We can explain at a cellular level and electrophysiological which is the basis of this [sickness behavior]," said Blank.
the study is important because it identifies a new channel of communication between the immune system and brain, Kelley said. Cunningham added that the data are consistent with the study of his group since last year, which involved the receptor for interferon-β in sickness behavior. But now researchers have gone much further by identifying the role of the interferon receptor in brain areas and revealing the involvement of CXCL10.
neuroimmunologist Robert Dantzer of the University of Texas MD Anderson Cancer Center in Houston is skeptical of the new mechanism, however. "The cytokines produced by immune cells act locally," he said. They are confined to places in the body where immune cells have been fighting against the virus and do not would go to the brain and trigger a disease behavior .
But researchers believe they are on track. An important question now, said Blank, is whether researchers can find ways to stop the behavior of the disease in patients autoimmune disease or cancer that receive treatment with interferon.
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