Diseased hearts to heal themselves in future

Diseased hearts to heal themselves in future

  10:08:00 AM    Science Lover

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Cellular reversion processes arise in diseases of the heart muscle, for example myocardial infarction and cardiomyopathy, which limit the fatal consequences for the organ. Scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim and the Schüchtermann Klinik in Bad Rothenfelde have identified a protein which fulfils a central task in this reversion process by stimulating the regression of individual heart muscle cells into their precursor cells. It is now planned to improve the self-healing powers of the heart with the help of this protein.

Cellular regression in diseased heart tissue with the help
of oncostatin M: The image shows heart muscles under
the fluorescence microscope. The myofibrils are stained
red, the cell nuclei blue.
Credit: MPI for Heart and Lung Research

In order to regenerate damaged heart muscle as caused by a heart attack, for example, the damaged muscle cells must be replaced by new ones. The number of cells to be replaced may be considerable, depending on the extent of the damage caused. Simpler vertebrates like the salamander adopt a strategy whereby surviving healthy heart muscle cells regress into an embryonic state. This process, which is known as dedifferentiation, produces cells which contain a series of stem cell markers and re-attain their cell division activity. Thus, new cells are produced which convert, in turn, into heart muscle cells. The cardiac function is then restored through the remodelling of the muscle tissue.

An optimised repair mechanism of this kind does not exist in humans. Although heart stem cells were discovered some time ago, exactly how and to what extent they play a role in cardiac repair is a matter of dispute. It has only been known for a few years that processes comparable to those found in the salamander even exist in mammals.

Thomas Braun's research group at the Max Planck Institute for Heart and Lung Research in Bad Nauheim has now discovered the molecule responsible for controlling this dedifferentiation of heart muscle cells in mammals. The scientists initially noticed the high concentration of oncostatin M in tissue samples from the hearts of patients suffering from myocardial infarction. It was already known that this protein is responsible for the dedifferentiation of different cell types, among other things. The researchers therefore treated cultivated heart muscle cells with oncostatin M in the laboratory and were then able to trace the regression of the cells live under the microscope: "Based on certain changes in the cells, we were able to see that almost all heart muscle cells had been dedifferentiated within six days of treatment with oncostatin M," explains Braun. "We were also able to demonstrate the presence of various stem cell markers in the cells. This should be understood as an indicator that these cells had been switched to a repair mode."

Using a mouse infarct model, the Max Planck researchers succeeded in demonstrating that oncostatin M actually does stimulate the repair of damaged heart muscle tissue as presumed. One of the two test groups had been modified genetically in advance to ensure that the oncostatin M could not have any effect in these animals. "The difference between the two groups was astonishing. Whereas in the group in which oncostatin M could take effect almost all animals were still alive after four weeks, 40 percent of the genetically modified mice had died from the effects of the infarction," says Braun. The reason for this was that oncostatin M ensured clearly quantifiable better cardiac function in the unmodified animals.

The scientists in Bad Nauheim would now like to find a way of using oncostatin M in treatment. The aim is to strengthen the self-healing powers of the damaged heart muscle and to enable the restoration of cardiac function for the first time. The downside, however, is that oncostatin M was also observed to be counterproductive and exacerbated the damage in an experiment on a chronically diseased heart. "We believe that oncostatin M has considerable potential for efficiently healing damaged heart muscle tissue. What we now need is to be able to pinpoint the precise window of application to prevent any possible negative effects," says Braun.
More information: Thomas Kubin, Jochen Pöling, Sawa Kostin, Praveen Gajawada, Stefan Hein, Wolfgang Rees, Astrid Wietelmann, Minoru Tanaka, Holger Lörchner, Silvia Schimanski, Marten Szibor, Henning Warnecke, Thomas Braun: Oncostatin M Is a Major Mediator of Cardiomyocyte Dedifferentiation and Remodeling. Cell Stem Cell 9, 420, 2011

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Scientists Measure Dream Content for the First Time: Dreams Activate the Brain in a Similar Way to Real Actions

Scientists Measure Dream Content for the First Time: Dreams Activate the Brain in a Similar Way to Real Actions

  9:51:00 PM    Science Lover

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The ability to dream is a fascinating aspect of the human mind. However, how the images and emotions that we experience so intensively when we dream form in our heads remains a mystery. Up to now it has not been possible to measure dream content. Max Planck scientists working with colleagues from the Charité hospital in Berlin have now succeeded, for the first time, in analysing the activity of the brain during dreaming.

Top: Patient in a functional magnetic resonance imaging machine. Bottom: Activity in the motor cortex during the movement of the hands while awake (left) and during a dreamed movement (right). Blue areas indicate the activity during a movement of the right hand, which is clearly demonstrated in the left brain hemisphere, while red regions indicate the corresponding left-hand movements in the opposite brain hemisphere. (Credit: © MPI of Psychiatry)

They were able to do this with the help of lucid dreamers, i.e. people who become aware of their dreaming state and are able to alter the content of their dreams. The scientists measured that the brain activity during the dreamed motion matched the one observed during a real executed movement in a state of wakefulness.

The research is published in the journal Current Biology.

Methods like functional magnetic resonance imaging have enabled scientists to visualise and identify the precise spatial location of brain activity during sleep. However, up to now, researchers have not been able to analyse specific brain activity associated with dream content, as measured brain activity can only be traced back to a specific dream if the precise temporal coincidence of the dream content and measurement is known. Whether a person is dreaming is something that could only be reported by the individual himself.

Scientists from the Max Planck Institute of Psychiatry in Munich, the Charité hospital in Berlin and the Max Planck Institute for Human Cognitive and Brain Sciences in Leipzig availed of the ability of lucid dreamers to dream consciously for their research. Lucid dreamers were asked to become aware of their dream while sleeping in a magnetic resonance scanner and to report this "lucid" state to the researchers by means of eye movements. They were then asked to voluntarily "dream" that they were repeatedly clenching first their right fist and then their left one for ten seconds.



This enabled the scientists to measure the entry into REM sleep -- a phase in which dreams are perceived particularly intensively -- with the help of the subject's electroencephalogram (EEG) and to detect the beginning of a lucid phase. The brain activity measured from this time onwards corresponded with the arranged "dream" involving the fist clenching. A region in the sensorimotor cortex of the brain, which is responsible for the execution of movements, was actually activated during the dream. This is directly comparable with the brain activity that arises when the hand is moved while the person is awake. Even if the lucid dreamer just imagines the hand movement while awake, the sensorimotor cortex reacts in a similar way.

The coincidence of the brain activity measured during dreaming and the conscious action shows that dream content can be measured. "With this combination of sleep EEGs, imaging methods and lucid dreamers, we can measure not only simple movements during sleep but also the activity patterns in the brain during visual dream perceptions," says Martin Dresler, a researcher at the Max Planck Institute for Psychiatry.

The researchers were able to confirm the data obtained using MR imaging in another subject using a different technology. With the help of near-infrared spectroscopy, they also observed increased activity in a region of the brain that plays an important role in the planning of movements. "Our dreams are therefore not a 'sleep cinema' in which we merely observe an event passively, but involve activity in the regions of the brain that are relevant to the dream content," explains Michael Czisch, research group leader at the Max Planck Institute for Psychiatry.

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