News

A new award from the CHDI Foundation will advance promising research that aims to slow the progression of Huntington's disease. The funding, anticipated to total more than $10.5 million over next five years, will help University of Rochester Medical Center (URMC) scientists develop a stem cell-based therapy that swaps sick brain cells for healthy ones.

The new award will go to the lab of Steve Goldman, M.D., Ph.D., the co-director of the URMC Center for Translational Neuromedicine, which has research operations in both Rochester and at the University of Copenhagen.

Huntington's is a hereditary neurodegenerative disease characterized by the loss of medium spiny neurons, a nerve cell in the brain that plays a critical role in motor control. As the disease progresses over time and more of these cells die, the result is involuntary movements, problems with coordination, and cognitive decline, depression, and often psychosis. There is currently no way to slow or modify this fatal disease.

The new award will support research that builds upon findings published by Goldman earlier this year in the journal Nature Communications showing that researchers were able to slow the progression of the disease in mice by transplanting healthy human support cells, called glial progenitor cells, into the animals' brains.

Maiken Nedergaard, M.D., D.M.Sc.

More than $4.5 million in new grants to the lab of University of Rochester Medical Center scientist Maiken Nedergaard, M.D., D.M.Sc., underscore the important role the brain's waste disposal system may play in a range of neurological disorders. The new awards will advance understanding of how small vessel disease and traumatic brain injury can give rise to cognitive and behavioral problems.

Nedergaard and her colleagues first unveiled the brain's unique method of removing waste -- dubbed the glymphatic system -- in a paper in Science Translational Medicine in 2012. The research revealed that the brain possesses a circulation network that piggybacks on blood vessels and uses cerebral spinal fluid to flush away waste products from brain tissue. Since that time, the team has gone on to show that the glymphatic system works primarily while we sleep, could be a key player in diseases like Alzheimer's, and is disrupted after traumatic brain injury.

New research in the journal Neuron reveals how the brain is able to meet its massive energy demands with a "just in time" system that delivers oxygen that fuels nerve cells. The findings could shed light on diseases like Alzheimer's and help explain the cognitive decline that accompanies the disease.

"Our brains require a tremendous amount of energy and in order to meet this demand the flow of blood must be precisely choreographed to ensure that oxygen is being delivered where it is needed and when it is needed," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the study. "This study demonstrates that microvessels in the brain play a key role in reacting to spikes in demand and accelerating the flow of blood to respond to neuronal activity."

Steven Goldman, professor of neurology, has been reappointed as codirector of the Center for Translational Neuromedicine and as the Dean Zutes Chair in Biology of the Aging Brain—both through June 30, 2020. Goldman also retains his joint appointments as professor of neurosurgery and as Distinguished Professor in Neurosciences.

Goldman is interested in cell genesis and neural regeneration in the adult brain. His lab focuses on the use of stem and progenitor cells for the treatment of neurodegenerative disorders such as Huntington’s Disease, as well as for the treatment of glial diseases such as the pediatric leukodystrophies and multiple sclerosis. He has published more than 250 papers in his field—more than 100 as first or senior author—as well as 20 issued patents with more pending.

Sleep is critical for rest and rejuvenation. A human being will actually die of sleep deprivation before starvation--it takes about two weeks to starve, but only 10 days to die if you go without sleep.

The CDC has also classified insufficient sleep as a public health concern. Those who don't get enough sleep are more likely to suffer from chronic diseases that include hypertension, diabetes, depression, obesity, and cancer.

It's thus vital to get enough shuteye, but it turns out your sleep position also has a significant impact on the quality of rest you get.

Now, a neuroscience study suggests that of all sleep positions, one is most helpful when it comes to efficiently cleaning out waste from the brain: sleeping on your side.

The study, published in the Journal of Neuroscience, used dynamic contrast-enhanced MRI to image the brain's "glymphatic pathway." This is the system by which cerebrospinal fluid filters through the brain and swaps with interstitial fluid (the fluid around all other cells in the body).

"It is interesting that the lateral [side] sleep position is already the most popular in humans and most animals--even in the wild," said University of Rochester's Maiken Nedergaard. "It appears that we have adapted the lateral sleep position to most efficiently clear our brain of the metabolic waste products that build up while we are awake."

Researchers have successfully reduced the symptoms and slowed the progression of Huntington’s disease in mice using healthy human brain cells. The findings, which were published today in the journal Nature Communications, could ultimately point to a new method to treat the disease.

The research entailed implanting the animals with human glia cells derived from stem cells. One of the roles of glia, an important support cell found in the brain, is to tend to the health of neurons and the study’s findings show that replacing sick mouse glia with healthy human cells blunted the progress of the disease and rescued nerve cells at risk of death.

“The role that glia cells play in the progression of Huntington’s disease has never really been explored,” said Steve Goldman, M.D., Ph.D., co-director of the University of Rochester Center for Translational Neuromedicine. “This study shows that these cells are not only important actors in the disease, but may also hold the key to new treatment strategies.”

A study out today in the journal Science sheds new light on the biological mechanisms that control the sleep-wake cycle. Specifically, it shows that a simple shift in the balance of chemicals found in the fluid that bathes and surrounds brain cells can alter the state of consciousness of animals.

The study, which focuses on a collection of ions that reside in the cerebral spinal fluid (CSF), found that not only do these changes play a key role in stimulating or dampening the activity of nerve cells, but they also appear to alter cell volume causing brain cells to shrink while we sleep, a process that facilitates the removal of waste.

"Understanding what drives arousal is essential to deciphering consciousness and the lack thereof during sleep," said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the study. "We found that the transition from wakefulness to sleep is accompanied by a marked and sustained change in the concentration of key extracellular ions and the volume of the extracellular space."

The current scientific consensus is that the brain is "woken up" by a set of neurotransmitters -- which include compounds such as acetylcholine, hypocretin, histamine, serotonin, noradrenaline, and dopamine -- that originate from structures deep within the brain and the brain stem. This cocktail of chemical messengers serve to activate -- or arouse -- a set of neurons in the cerebral cortex and other parts of the brain responsible for memory, thinking, and learning, placing the brain in a state of wakefulness.