Press Releases & Research Commentary
November 17, 2013
A study out today in the journal Nature Medicine suggests a potential new treatment for the seizures that often plague children with genetic metabolic disorders and individuals undergoing liver failure. The discovery hinges on a new understanding of the complex molecular chain reaction that occurs when the brain is exposed to too much ammonia.
The study shows that elevated levels of ammonia in the blood overwhelm the brain's defenses, ultimately causing nerve cells to become overexcited. The researchers have also discovered that bumetanide - a diuretic drug used to treat high blood pressure - can restore normal electrical activity in the brains of mice with the condition and prevent seizures.
Ammonia is a ubiquitous waste product of regular protein metabolism, but it can accumulate in toxic levels in individuals with metabolic disorders,said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article.
It appears that the key to preventing the debilitating neurological effects of ammonia toxicity is to correct a molecular malfunction which causes nerve cells in the brain to become chemically unbalanced.
October 17, 2013
The US team believe the
waste removal systemis one of the fundamental reasons for sleep. Their study, in the journal Science, showed brain cells shrink during sleep to open up the gaps between neurons and allow fluid to wash the brain clean. They also suggest that failing to clear away some toxic proteins may play a role in brain disorders.
One big question for sleep researchers is why do animals sleep at all when it leaves them vulnerable to predators? It has been shown to have a big role in the fixing of memories in the brain and learning, but a team at the University of Rochester Medical Centre believe that
houseworkmay be one of the primary reasons for sleep.
The brain only has limited energy at its disposal and it appears that it must choose between two different functional states - awake and aware or asleep and cleaning up,said researcher Dr Maiken Nedergaard.
You can think of it like having a house party. You can either entertain the guests or clean up the house, but you can't really do both at the same time.
August 19, 2013
Copper appears to be one of the main environmental factors that trigger the onset and enhance the progression of Alzheimer's disease by preventing the clearance and accelerating the accumulation of toxic proteins in the brain. That is the conclusion of a study appearing today in the journal Proceedings of the National Academy of Sciences.
It is clear that, over time, copper's cumulative effect is to impair the systems by which amyloid beta is removed from the brain,said Rashid Deane, Ph.D., a research professor in the University of Rochester Medical Center Department of Neurosurgery, member of the Center for Translational Neuromedicine, and the lead author of the study.
This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer's disease.
August 10, 2013
NGP Student, Helen Wei, Awarded the HHMI Med-Into-Grad Fellowship
June 27, 2013
In a perspective piece appearing today in the journal Science, researchers at University of Rochester Medical Center 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 barrierwas 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.
March 7, 2013
A human glial cell (green) among normal mouse glial cells (red). The human cell is larger, sends out more fibers and has more connections than do mouse cells. Mice with this type of human cell implanted in their brains perform better on learning and memory tests than do typical mice.
For more than a century, neurons have been the superstars of the brain. Their less glamorous partners, glial cells, can't send electric signals, and so they've been mostly ignored. Now scientists have injected some human glial cells into the brains of newborn mice. When the mice grew up, they were faster learners. The study, published Thursday in Cell Stem Cell by Maiken Nedergaard, M.D., D.M.Sc. and Dr. Steven Goldman, M.D., Ph.D., not only introduces a new tool to study the mechanisms of the human brain, it supports the hypothesis that glial cells - and not just neurons - play an important role in learning.
Today, glial research and Dr. Goldman were featured on National Public Radio (NPR) speaking about the glial research that is outlined in this current publication.
I can't tell the differences between a neuron from a bird or a mouse or a primate or a human,says Goldman, glial cells are easy to tell apart.
Human glial cells - human astrocytes - are much larger than those of lower species. They have more fibers and they send those fibers out over greater distances.
In collaboration with the Nedergaard Lab, newborn mice had some human glial cells injected into their brains. The mice grew up, and so did the human glial cells. The cells spread through the mouse brain, integrating perfectly with mouse neurons and, in some areas, outnumbering their mouse counterparts. All the while Goldman says the glial cells maintained their human characteristics.
March 7, 2013
Glial cells – a family of cells found in the human central nervous system and, until recently, considered mere
housekeepers– now appear to be essential to the unique complexity of the human brain. Scientists reached this conclusion after demonstrating that when transplanted into mice, these human cells could influence communication within the brain, allowing the animals to learn more rapidly.
The study, out today in the journal Cell Stem Cell, suggests that the evolution of a subset of glia called astrocytes – which are larger and more complex in humans than other species – may have been one of the key events that led to the higher cognitive functions that distinguish us from other species.
The role of the astrocyte is to provide the perfect environment for neural transmission,said Maiken Nedergaard, M.D., D.M.Sc., co-senior author of the study and director, along with Dr. Steven Goldman, M.D., Ph.D., of the URMC Center for Translational Neuromedicine.
As the same time, we've observed that as these cells have evolved in complexity, size, and diversity – as they have in humans – brain function becomes more and more complex.
February 22, 2013
A novel way to image the entire brain's glymphatic pathway, a dynamic process that clears waste and solutes from the brain that otherwise might build-up and contribute to the development of Alzheimer's disease, may provide the basis for a new strategy to evaluate disease susceptibility, according to a research paper published online in the Journal of Clinical Investigation. Through contrast enhanced magnetic resonance imaging (MRI) and other tools, a Stony Brook University-led research team successfully mapped this brain-wide pathway and identified key anatomical clearance routes of brain waste.
In their article titled
Brain-wide pathway for waste clearance captured by contrast enhanced MRI,Principal Investigator Helene Benveniste, MD, PhD, a Professor in the Departments of Anesthesiology and Radiology at Stony Brook University School of Medicine, and colleagues built upon a previous finding by Jeffrey Iliff, PhD, and Maiken Nedergaard, MD, PhD, from University of Rochester that initially discovered and defined the glymphatic pathway, where cerebral spinal fluid (CSF) filters through the brain and exchanges with interstitial fluid (ISF) to clear waste, similar to the way lymphatic vessels clear waste from other organs of the body. Despite the discovery of the glymphatic pathway, researchers could not visualize the brain wide flow of this pathway with previous imaging techniques.
February 20, 2013
The brain and spinal cord are surrounded by cerebrospinal fluid, which provides a mechanically stable environment for these delicate structures against the forces of gravity and sudden acceleration and deceleration. Neurons and glia comprising the parenchyma of the brain are enveloped in their microenvironment by interstitial fluid. Interstitial fluid has long been considered to be unaffected by the production and flow of cerebrospinal fluid outside the brain parenchyma. However, two recent papers by Iliff et al. demonstrate that cerebrospinal fluid enters the deep substance of the brain, mixes with the interstitial fluid surrounding neurons and glia, and plays an important role in the exchange and clearance of molecules in the interstitial space of the central nervous system.
January 10, 2013
A new study out today in the journal Science turns two decades of understanding about how brain cells communicate on its head. The study demonstrates that the tripartite synapse – a model long accepted by the scientific community and one in which multiple cells collaborate to move signals in the central nervous system – does not exist in the adult brain.
Our findings demonstrate that the tripartite synaptic model is incorrect,said Maiken Nedergaard, M.D., D.M.Sc., lead author of the study and co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine.
This concept does not represent the process for transmitting signals between neurons in the brain beyond the developmental stage.
- Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices. Glia. 62, 78-95. (2014 Jan 01).
- Is potassium a ubiquitous mediator of vasodilation in the central nervous system? Biophys J. 105, 2238-9. (2013 Nov 19).
- Ammonia triggers neuronal disinhibition and seizures by impairing astrocyte potassium buffering. Nat Med. In press. (2013 Nov 17).