Epilepsy that does not respond to drugs can be halted in adult mice by transplanting a specific type of cell into the brain, UC San Francisco researchers have discovered, raising hope that a similar treatment might work in severe forms of human epilepsy.
UCSF scientists controlled seizures in epileptic mice with a one-time transplantation of medial ganglionic eminence (MGE) cells, which inhibit signaling in overactive nerve circuits, into the hippocampus, a brain region associated with seizures, as well as with learning and memory. Other researchers had previously used different cell types in rodent cell transplantation experiments and failed to stop seizures.
Cell therapy has become an active focus of epilepsy research, in part because current medications, even when effective, only control symptoms and not underlying causes of the disease, according to Scott C. Baraban, PhD, who holds the William K. Bowes Jr. Endowed Chair in Neuroscience Research at UCSF and led the new study. In many types of epilepsy, he said, current drugs have no therapeutic value at all.
"Our results are an encouraging step toward using inhibitory neurons for cell transplantation in adults with severe forms of epilepsy," Baraban said. "This procedure offers the possibility of controlling seizures and rescuing cognitive deficits in these patients."
The findings, which are the first ever to report stopping seizures in mouse models of adult human epilepsy, will be published online May 5 in the journal Nature Neuroscience.
During epileptic seizures, extreme muscle contractions and, often, a loss of consciousness can cause seizure sufferers to lose control, fall and sometimes be seriously injured. The unseen malfunction behind these effects is the abnormal firing of many excitatory nerve cells in the brain at the same time.
In the UCSF study, the transplanted inhibitory cells quenched this synchronous, nerve-signaling firestorm, eliminating seizures in half of the treated mice and dramatically reducing the number of spontaneous seizures in the rest. Robert Hunt, PhD, a postdoctoral fellow in the Baraban lab, guided many of the key experiments.
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【Time4】
In another encouraging step, UCSF researchers reported May 2 that they found a way to reliably generate human MGE-like cells in the laboratory, and that, when transplanted into healthy mice,the cells similarly spun off functional inhibitory nerve cells. That research can be found online in the journal Cell Stem Cell.
In many forms of epilepsy, loss or malfunction of inhibitory nerve cells within the hippocampus plays a critical role. MGE cells are progenitor cells that form early within the embryo and are capable of generating mature inhibitory nerve cells called interneurons. In the Baraban-led UCSF study, the transplanted MGE cells from mouse embryos migrated and generated interneurons, in effect replacing the cells that fail in epilepsy. The new cells integrated into existing neural circuits in the mice, the researchers found.
"These cells migrate widely and integrate into the adult brain as new inhibitory neurons," Baraban said. "This is the first report in a mouse model of adult epilepsy in which mice that already were having seizures stopped having seizures after treatment."
The mouse model of disease that Baraban's lab team worked with is meant to resemble a severe and typically drug-resistant form of human epilepsy called mesial temporal lobe epilepsy, in which seizures are thought to arise in the hippocampus. In contrast to transplants into the hippocampus, transplants into the amygdala, a brain region involved in memory and emotion, failed to halt seizure activity in this same mouse model, the researcher found.
Temporal lobe epilepsy often develops in adolescence, in some cases long after a seizure episode triggered during early childhood by a high fever. A similar condition in mice can be induced with a chemical exposure, and in addition to seizures, this mouse model shares other pathological features with the human condition, such as loss of cells in the hippocampus, behavioral alterations and impaired problem solving.
In the Nature Neuroscience study, in addition to having fewer seizures, treated mice became less abnormally agitated, less hyperactive, and performed better in water-maze tests.
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Article III (Check the title later)
Brighter Clouds, Cooler Climate? Organic Vapors Affect Clouds, Leading to Previously Unidentified Climate Cooling
【Time5】
University of Manchester scientists, writing in the journal Nature Geoscience, have shown that natural emissions and humanmade pollutants can both have an unexpected cooling effect on Earth's climate by making clouds brighter.
Clouds are made of water droplets, condensed onto tiny particles suspended in the air. When the air is humid enough, the particles swell into cloud droplets. It has been known for some decades that the number of these particles and their size control how bright the clouds appear from the top, controlling the efficiency with which clouds scatter sunlight back into space. A major challenge for climate science is to understand and quantify these effects which have a major impact in polluted regions.
The tiny seed particles can either be natural (for example, sea spray or dust) or humanmade pollutants (from vehicle exhausts or industrial activity). These particles often contain a large amount of organic material and these compounds are quite volatile, so in warm conditions exist as a vapour (in much the same way as a perfume is liquid but gives off an aroma when it evaporates on warm skin).
The researchers found that the effect acts in reverse in the atmosphere as volatile organic compounds from pollution or from the biosphere evaporate and give off characteristic aromas, such as the pine smells from forest, but under moist cooler conditions where clouds form, the molecules prefer to be liquid and make larger particles that are more effective seeds for cloud droplets.
"We discovered that organic compounds such as those formed from forest emissions or from vehicle exhaust, affect the number of droplets in a cloud and hence its brightness, so affecting climate," said study author Professor Gordon McFiggans, from the University of Manchester's School of Earth, Atmospheric and Environmental Sciences.
"We developed a model and made predictions of a substantially enhanced number of cloud droplets from an atmospherically reasonable amount of organic gases.
"More cloud droplets lead to brighter cloud when viewed from above, reflecting more incoming sunlight. We did some calculations of the effects on climate and found that the cooling effect on global climate of the increase in cloud seed effectiveness is at least as great as the previously found entire uncertainty in the effect of pollution on clouds."
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Part II Obstacle
Article IV (Check the title later)
As Climate Changes, Boreal Forests to Shift North and Relinquish More Carbon Than Expected
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It's difficult to imagine how a degree or two of warming will affect a location. Will it rain less? What will happen to the area's vegetation?
New Berkeley Lab research offers a way to envision a warmer future. It maps how Earth's myriad climates -- and the ecosystems that depend on them -- will move from one area to another as global temperatures rise.
The approach foresees big changes for one of the planet's great carbon sponges. Boreal forests will likely shift north at a steady clip this century. Along the way, the vegetation will relinquish more trapped carbon than most current climate models predict.
The research is published online May 5 in the journal Nature Geoscience.
Boreal ecosystems encircle the planet's high latitudes, covering swaths of Canada, Europe, and Russia in coniferous trees and wetlands. This vegetation stores vast amounts of carbon, keeping it out of the atmosphere where it can contribute to climate change.
Scientists use incredibly complex computer simulations called Earth system models to predict the interactions between climate change and ecosystems such as boreal forests. These models show that boreal habitat will expand poleward in the coming decades as regions to their north become warmer and wetter. This means that boreal ecosystems are expected to store even more carbon than they do today.
But the Berkeley Lab research tells a different story. The planet's boreal forests won't expand poleward. Instead, they'll shift poleward. The difference lies in the prediction that as boreal ecosystems follow the warming climate northward, their southern boundaries will be overtaken by even warmer and drier climates better suited for grassland.
And that's a key difference. Grassland stores a lot of carbon in its soil, but it accumulates at a much slower rate than is lost from diminishing forests.
"I found that the boreal ecosystems ringing the globe will be pushed north and replaced in their current location by what's currently to their south. In some places, that will be forest, but in other places it will be grassland," says Charles Koven, a scientist in Berkeley Lab's Earth Sciences Division who conducted the research.
"Most Earth system models don't predict this, which means they overestimate the amount of carbon that high-latitude vegetation will store in the future," he adds.
Koven's results come from a new way of tracking global warming's impact on Earth's mosaic of climates. The method is based on the premise that as temperatures rise, a location's climate will be replaced by a similar but slightly warmer climate from a nearby area. The displaced climate will in turn shift to another nearby location with a slightly cooler climate. It's as if climate change forces warmer climates to flow toward cooler areas, making everywhere warmer over time.
This approach can help determine where a given climate is going to in the future, and where a given climate will come from.
Koven applied this approach to 21 climate models. He used simulations that depict a middle-of-the-road climate change scenario, meaning the range of warming by the end of this century is 1.0°C to 2.6°C above a 1986 to 2005 baseline.
Climate models divide the planet into gridcells that cover tens or hundreds of square kilometers. In each model, Koven identified which gridcells in a warmer climate have a nearby gridcell with a similar climate in terms of average monthly temperature and precipitation. A good match, for example, is a neighboring gridcell that has similar rainfall patterns but is slightly warmer in the summer and winter.
Koven then calculated the speed at which a gridcell's climate will shift toward its matching gridcell over the next 80 years. He also investigated how this shift will transport the carbon stored in the vegetation that grows in the gridcell's climate.
In general, he found that climates move toward the poles and up mountain slopes. In parts of South America, warmer climates march westward up the Andes. In the southern latitudes, warmer climates head south.
But the most dramatic changes occur in the higher latitudes. Here, boreal ecosystems will have to race poleward in order to keep up with their climates. They'll also be encroached by warmer climates from the south. By the end of this century, a forest near Alberta, Canada will have to move 100 miles north in order to maintain its climate. And it will gain a climate that is now located 100 miles to the south.
Forests can't adapt this quickly, however, meaning that in the short-term they'll be stressed. And in the long-term they'll be forced to move north and give up their southern regions to grassland.
Only one of the Earth system models shows this precipitous loss of carbon in southern boreal forests. Koven says that's because most models don't account for random events such as fire, drought, and insects that kill already-stressed trees. His "climate analogue" approach does account for these events because they're implicit in the spatial distribution of ecosystems.
In addition, Earth system models predict carbon loss by placing vegetation at a given point, and then changing various climate properties above it.
"But this approach misses the fact that the whole forest might shift to a different place," says Koven.
This research was supported by the U.S. Department of Energy's Office of Science.
Explore the “Climate Analog Tracker,” an online tool that enables users to see how climates may shift in the decades to come.
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发表于 2013-5-6 16:32:12
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