Brain's 'Garbage Truck' May Hold Key to Treating Alzheimer's and Other Disorders

In a perspective piece appearing today in the journal Science, researchers at University of Rochester Medical Center (URMC) point to a newly discovered system by which the brain removes waste as a potentially powerful new tool to treat neurological disorders like Alzheimer's disease. In fact, scientists believe that some of these conditions may arise when the system is not doing its job properly.

Essentially all neurodegenerative diseases are associated with the accumulation of cellular waste products," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the URMC Center for Translational Neuromedicine and author of the article. "Understanding and ultimately discovering how to modulate the brain's system for removing toxic waste could point to new ways to treat these diseases."

The body defends the brain like a fortress and rings it with a complex system of gateways that control which molecules can enter and exit. While this "blood-brain barrier" was first described in the late 1800s, scientists are only now just beginning to understand the dynamics of how these mechanisms function. In fact, the complex network of waste removal, which researchers have dubbed the glymphatic system, was only first disclosed by URMC scientists last August in the journal Science Translational Medicine.

The removal of waste is an essential biological function and the lymphatic system -- a circulatory network of organs and vessels -- performs this task in most of the body. However, the lymphatic system does not extend to the brain and, consequently, researchers have never fully understood what the brain does its own waste. Some scientists have even speculated that these byproducts of cellular function where somehow being "recycled" by the brain's cells.

One of the reasons why the glymphatic system had long eluded comprehension is that it cannot be detected in samples of brain tissue. The key to discovering and understanding the system was the advent of a new imaging technology called two-photon microscopy which enables scientists to peer deep within the living brain. Using this technology on mice, whose brains are remarkably similar to humans, Nedergaard and her colleagues were able to observe and document what amounts to an extensive, and heretofore unknown, plumbing system responsible for flushing waste from throughout the brain.

The brain is surrounded by a membrane called the arachnoid and bathed in cerebral spinal fluid (CSF). CSF flows into the interior of the brain through the same pathways as the arteries that carry blood. This parallel system is akin to a donut shaped pipe within a pipe, with the inner ring carrying blood and the outer ring carrying CSF. The CSF is draw into brain tissue via a system of conduits that are controlled by a type support cells in the brain known as glia, in this case astrocytes. The term glymphatic was coined by combining the words glia and lymphatic.

The CSF is flushed through the brain tissue at a high speed sweeping excess proteins and other waste along with it. The fluid and waste are exchanged with a similar system that parallels veins which carries the waste out of the brain and down the spine where it is eventually transferred to the lymphatic system and from there to the liver, where it is ultimately broken down.

While the discovery of the glymphatic system solved a mystery that had long baffled the scientific community, understanding how the brain removes waste -- both effectively and what happens when this system breaks down -- has significant implications for the treatment of neurological disorders.

One of the hallmarks of Alzheimer's disease is the accumulation in the brain of the protein beta amyloid. In fact, over time these proteins amass with such density that they can be observed as plaques on scans of the brain. Understanding what role the glymphatic system plays in the brain's inability to break down and remove beta amyloid could point the way to new treatments. Specifically, whether certainly key 'players' in the glymphatic system, such as astrocytes, can be manipulated to ramp up the removal of waste.

"The idea that 'dirty brain' diseases like Alzheimer may result from a slowing down of the glymphatic system as we age is a completely new way to think about neurological disorders," said Nedergaard. "It also presents us with a new set of targets to potentially increase the efficiency of glymphatic clearance and, ultimately, change the course of these conditions."

Source: Science Daily


Study of Oceans' Past Raises Worries About Their Future

The ocean the Titanic sailed through just over 100 years ago was very different from the one we swim in today. Global warming is increasing ocean temperatures and harming marine food webs. Nitrogen run-off from fertilizers is causing coastal dead zones. A McGill-led international research team has now completed the first global study of changes that occurred in a crucial component of ocean chemistry, the nitrogen cycle, at the end of the last ice age. The results of their study confirm that oceans are good at balancing the nitrogen cycle on a global scale. But the data also shows that it is a slow process that may take many centuries, or even millennia, raising worries about the effects of the scale and speed of current changes in the ocean.

"For the first time we can quantify how oceans responded to slow, natural climate warming as the world emerged from the last ice age," says Prof. Eric Galbraith from McGill University's Department of Earth and Oceanic Sciences, who led the study. "And what is clear is that there is a strong climate sensitivity in the ocean nitrogen cycle."

The nitrogen cycle is a key component of the global ocean metabolism. Like the proteins that are essential to human health, nitrogen is crucial to the health of oceans. And just as proteins are carried by the blood and circulate through the body, the nitrogen in the ocean is kept in balance by marine bacteria through a complicated cycle that keeps the ocean healthy. The phytoplankton (microscopic organisms at the base of the food chain) 'fix' nitrogen in the shallow, sunlit waters of the ocean, and then as they die and sink, nitrogen is eliminated (a process known as 'DE nitrification') in dark, oxygen-poor pockets of the ocean depths.

Using sediment gathered from the ocean floor in different areas of the world, the researchers were able to confirm that as the ice sheets started melting and the climate warmed up at the end of the last ice age, 18,000 years ago, the marine nitrogen cycle started to accelerate. The ocean had stabilized itself in its new, warmer state, in which the overall nitrogen cycle was running faster, by about 8,000 years ago. Given the current dramatic rate of change in the ocean nitrogen cycle the researchers are not sure how long it will take for marine ecosystems to adapt.

"We are changing the planet in ways we are not even aware of," says Galbraith. "You wouldn't think that putting carbon dioxide into the atmosphere would change the amount of nitrogen available to fish in the ocean, but it clearly does. It is important to realize just how interconnected everything is."

Source: Science Daily


New Tasks Become as Simple as Waving a Hand With Brain-Computer Interfaces

Small electrodes placed on or inside the brain allow patients to interact with computers or control robotic limbs simply by thinking about how to execute those actions. This technology could improve communication and daily life for a person who is paralyzed or has lost the ability to speak from a stroke or neurodegenerative disease.

University of Washington researchers have demonstrated that when humans use this technology -- called a brain-computer interface -- the brain behaves much like it does when completing simple motor skills such as kicking a ball, typing or waving a hand. Learning to control a robotic arm or a prosthetic limb could become second nature for people who are paralyzed.

"What we're seeing is that practice makes perfect with these tasks," said Rajesh Rao, a UW professor of computer science and engineering and a senior researcher involved in the study. "There's a lot of engagement of the brain's cognitive resources at the very beginning, but as you get better at the task, those resources aren't needed anymore and the brain is freed up."

Rao and UW collaborators Jeffrey Ojemann, a professor of neurological surgery, and Jeremiah Wander, a doctoral student in bioengineering, published their results online June 10 in the Proceedings of the National Academy of Sciences.

In this study, seven people with severe epilepsy were hospitalized for a monitoring procedure that tries to identify where in the brain seizures originate. Physicians cut through the scalp, drilled into the skull and placed a thin sheet of electrodes directly on top of the brain. While they were watching for seizure signals, the researchers also conducted this study.

The patients were asked to move a mouse cursor on a computer screen by using only their thoughts to control the cursor's movement. Electrodes on their brains picked up the signals directing the cursor to move, sending them to an amplifier and then a laptop to be analyzed. Within 40 milliseconds, the computer calculated the intentions transmitted through the signal and updated the movement of the cursor on the screen.

Researchers found that when patients started the task, a lot of brain activity was centered in the prefrontal cortex, an area associated with learning a new skill. But after often as little as 10 minutes, frontal brain activity lessened, and the brain signals transitioned to patterns similar to those seen during more automatic actions.

"Now we have a brain marker that shows a patient has actually learned a task," Ojemann said. "Once the signal has turned off, you can assume the person has learned it."

While researchers have demonstrated success in using brain-computer interfaces in monkeys and humans, this is the first study that clearly maps the neurological signals throughout the brain. The researchers were surprised at how many parts of the brain were involved.

"We now have a larger-scale view of what's happening in the brain of a subject as he or she is learning a task," Rao said. "The surprising result is that even though only a very localized population of cells is used in the brain-computer interface, the brain recruits many other areas that aren't directly involved to get the job done."

Several types of brain-computer interfaces are being developed and tested. The least invasive is a device placed on a person's head that can detect weak electrical signatures of brain activity. Basic commercial gaming products are on the market, but this technology isn't very reliable yet because signals from eye blinking and other muscle movements interfere too much.

A more invasive alternative is to surgically place electrodes inside the brain tissue itself to record the activity of individual neurons. Researchers at Brown University and the University of Pittsburgh have demonstrated this in humans as patients, unable to move their arms or legs, have learned to control robotic arms using the signal directly from their brain.

The UW team tested electrodes on the surface of the brain, underneath the skull. This allows researchers to record brain signals at higher frequencies and with less interference than measurements from the scalp. A future wireless device could be built to remain inside a person's head for a longer time to be able to control computer cursors or robotic limbs at home.

Source: Science Daily


Black hole caught napping after meal

A black hole 11 million light-years away has gone dormant, a decade after being spotted consuming cosmic debris.

The black hole lies at the center of the Sculptor galaxy, a so-called starburst galaxy where stars are being born at a prodigious rate.

But the X-ray light corresponding to a black hole's snack has dimmed markedly.

The find, to appear in Astrophysical Journal, has mystified astronomers because star formation and black hole activity tend to go hand-in-hand.

The Sculptor galaxy - also known as NGC 253 - hosts a central black hole with a mass some five million times that of our Sun - a quarter again as plump as the black hole at the center of our own Milky Way galaxy.

In 2003, researchers using the Chandra space telescope caught sight of the X-rays that correspond to matter spiraling down into the black hole and heating up to millions of degrees.

    Black holes are incredibly dense objects with gravity strong enough to trap even light

    A 'medium' black hole could have the mass of 1,000 Suns but be no bigger than Earth

    Supermassive black holes are thought to be at the center of most large galaxies - including ours

But as of mid-2012, the X-ray sky has a new observer: a space telescope called the Nuclear Spectroscopic Telescope Array or Nustar, already a successful black-hole hunter.

Nustar can spot even higher-energy X-rays than Chandra, and in late 2012, both telescopes were trained on NGC 253 - with the surprise finding that the X-ray emission seems to have stopped.

"Black holes feed off surrounding accretion disks of material. When they run out of this fuel, they go dormant," said Ann Hornschemeier of Nasa's Goddard Space Flight Center, a co-author on the new study.

"NGC 253 is somewhat unusual because the giant black hole is asleep in the midst of tremendous star-forming activity all around it".

The subtle interplay between black hole activity and the birth rate of new stars remains somewhat mysterious, but Bret Lehmer of Nasa's Goddard Space Flight Center, lead author on the paper, said that the Sculptor galaxy could shed new light on these dark galactic corners.

"Periodic observations with both Chandra and Nustar should tell us unambiguously if the black hole wakes up again. If this happens in the next few years, we hope to be watching," he said.

Source :BBC


Biological clocks 'beat quicker' in cities

City living could have a major impact on the biological clocks of humans and animals, a new study has found.

Researchers measured the circadian rhythms - the 24-hour cycle of biological activity - of urban and rural blackbirds in southern Germany.

German and Scottish researchers found the city birds woke up earlier and rested less than forest dwelling birds.

The team has raised the possibility the differences could be the result of micro-evolutionary changes.

The study, which has been published in the journal Proceedings of the Royal Society B, was carried out by Glasgow University and the Max Planck Institute for Ornithology in Germany.

A number of adult male European blackbirds were captured from Munich and a nearby rural forest.

Each bird was equipped with a lightweight radio-transmitter which monitored their daily levels of activity in the wild for 10 days before they were recaptured.

"Our work shows for the first time that that when sharing human habitats, a wild animal species has a different internal clock".

They were then kept in light-proofed, sound-insulated chambers and their circadian rhythms were measured under constant conditions

Once the tests were complete the birds were returned to the wild

Dr Barbara Helm, from Glasgow University's institute of biodiversity, animal health and comparative medicine, said: "We found that the rhythms of urban birds in the wild differ significantly from their forest counterparts.

"On average, they began their daily activities around 30 minutes before dawn, while forest birds began their day as the sun rose.

"The city birds ended their days around nine minutes later, meaning they were active for about 40 minutes longer each day".

Dr Helm said in "constant laboratory conditions" the circadian rhythms of urban birds were clearly altered".

"There seems to be a different beat to city life", she said. "City clocks were also less persistent, especially in the business district".

The team said its research added "to a growing consensus" that towns and cities "have a profound effect on the internal clocks" of humans and animals

It said further study was needed to determine whether these changes could lead to increased health problems or were related to better function in urban areas.

Dr Helm added: "Previous research undertaken by other researchers has suggested strong links in humans between disrupted sleep patterns and an increased incidence of depression and diseases including obesity and some types of cancers.

"Our work shows for the first time that when sharing human habitats, a wild animal species has a different internal clock.

"We'd be keen to find out the costs and benefits of modifying biological rhythms in blackbirds and other animals commonly found in our cities. This may help us to better understand the challenges of coping with urban life".

The researchers have raised the possibility the differences in the biological rhythms could be the result of micro-evolutionary changes in response to urban phenomena such as artificial light and increased noise levels.