Posts tagged brain

Borrowing from microfabrication techniques used in the semiconductor industry, MIT and Harvard Medical School (HMS) engineers have developed a simple and inexpensive way to create three-dimensional brain tissues in a lab dish.

The new technique yields tissue constructs that closely mimic the cellular composition of those in the living brain, allowing scientists to study how neurons form connections and to predict how cells from individual patients might respond to different drugs. The work also paves the way for developing bioengineered implants to replace damaged tissue for organ systems, according to the researchers.

"We think that by bringing this kind of control and manipulation into neurobiology, we can investigate many different directions," says Utkan Demirci, an assistant professor in the Harvard-MIT Division of Health Sciences and Technology (HST).

Demirci and Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at MIT’s Media Lab and McGovern Institute, are senior authors of a paper describing the new technique, which appears in the Nov. 27 online edition of the journal Advanced Materials. The paper’s lead author is Umut Gurkan, a postdoc at HST, Harvard Medical School and Brigham and Women’s Hospital.

(Source: eurekalert.org)

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Reduced production of myelin, a type of protective nerve fiber that is lost in diseases like multiple sclerosis, may also play a role in the development of mental illness, according to researchers at the Graduate School of Biomedical Sciences at Mount Sinai School of Medicine. The study is published in the journal Nature Neuroscience.

Myelin is an insulating material that wraps around the axon, the threadlike part of a nerve cell through which the cell sends impulses to other nerve cells. New myelin is produced by nerve cells called oligodendrocytes both during development and in adulthood to repair damage in the brain of people with diseases such as multiple sclerosis (MS).

A new study led by Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics; and Neurology at Mount Sinai, determined that depriving mice of social contact reduced myelin production, demonstrating that the formation of new oligodendrocytes is affected by environmental changes. This research provides further support to earlier evidence of abnormal myelin in a wide range of psychiatric disorders, including autism, anxiety, schizophrenia and depression.

“We knew that a lack of social interaction early in life impacted myelination in young animals but were unsure if these changes would persist in adulthood,” said Dr. Casaccia, who is also Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at Mount Sinai School of Medicine. “Social isolation of adult mice causes behavioral and structural changes in neurons, but this is the first study to show that it causes myelin dysfunction as well.”

Dr. Casaccia’s team isolated adult mice to determine whether new myelin formation was compromised. After eight weeks, they found that the isolated mice showed signs of social withdrawal. Subsequent brain tissue analyses indicated that the socially isolated mice had lower-than-normal levels of myelin-forming oligodendrocytes in the prefrontal cortex, but not in other areas of the brain. The prefrontal cortex controls complex emotional and cognitive behavior.

The researchers also found changes in chromatin, the packing material for DNA. As a result, the DNA from the new oligodendrocytes was unavailable for gene expression.

After observing the reduction in myelin production in socially-isolated mice, Dr. Casaccia’s team then re-introduced these mice into a social group. After four weeks, the social withdrawal symptoms and the gene expression changes were reversed.

“Our study demonstrates that oligodendrocytes generate new myelin as a way to respond to environmental stimuli, and that myelin production is significantly reduced in social isolation,” said Dr. Casaccia. “Abnormalities occur in people with psychiatric conditions characterized by social withdrawal. Other disorders characterized by myelin loss, such as MS, often are associated with depression. Our research emphasizes the importance of maintaining a socially stimulating environment in these instances.”

At Mount Sinai, Dr. Casaccia’s laboratory is studying oligodendrocyte formation to identify therapeutic targets for myelin repair. They are screening newly-developed pharmacological compounds in brain cells from rodents and humans for their ability to form new myelin.

(Source: newswise.com)

Scientists have revealed the minutely detailed pain map of the hand that is contained within our brains, shedding light on how the brain makes us feel discomfort and potentially increasing our understanding of the processes involved in chronic pain. 

The map, uncovered by scientists at UCL, is the first to reveal how finely-tuned the brain is to pain. Published in the Journal of Neuroscience, the study uses fMRI techniques in conjunction with laser stimuli to the fingers to plot the exact response to pain across areas of the brain.

“The results reveal that pain can be finely mapped in the brain,” said lead author Dr Flavia Mancini (UCL Institute of Cognitive Neuroscience). “While many studies have examined the brain response to pain before, our study is the first to map pain responses for the individual digits of the human hand.”

Using an fMRI brain imaging technique originally created to map the visual field, the researchers were able to distinguish the brain’s responses to painful laser heat stimuli on each finger in seven healthy participants, and to study their organisation in the brain. 

This enabled the team to produce a fine-grained map showing how pain in the right hand results in certain parts of the brain being activated in the primary somatosensory cortex, an area in the left hemisphere of the brain which is involved in processing bodily information.

When comparing this pain map to ones generated by non-painful touch to the right hand, the researchers found that the two were very similar, with each map aligning with one another in each of the seven volunteers tested.

“The cells in the skin that respond to pain and the cells that respond to touch have very different structures and distributions, so we were surprised to find that the maps of pain and of touch were so similar in the brain,” said Dr Mancini. “The striking alignment of pain and touch maps suggests powerful interactions between the two systems.”

The pain maps could be used to provide markers for the location of pain in the human brain, enabling clinicians to see how patients’ brains reorganise following chronic pain. 

“We know that the organisation of other sensory maps in the brain is altered in patients with chronic pain,” said Professor Patrick Haggard (UCL Institute of Cognitive Neuroscience). “Our method could next be used to track the reorganisation of brain maps that occurs in chronic pain, providing new insights into how the brain makes us feel pain. Therefore, measuring the map for pain itself is highly important.”

(Source: ucl.ac.uk)

A small molecule known to regulate white blood cells has a surprising second role in protecting brain cells from the deleterious effects of stroke, Johns Hopkins researchers report. The molecule, microRNA-223, affects how cells respond to the temporary loss of blood supply brought on by stroke — and thus the cells’ likelihood of suffering permanent damage.

“We set out to find a small molecule with very specific effects in the brain, one that could be the target of a future stroke treatment,” says Valina Dawson, Ph.D., a professor in the Johns Hopkins University School of Medicine’s Institute for Cell Engineering. “What we found is this molecule involved in immune response, which also acts in complex ways on the brain. This opens up a suite of interesting questions about what microRNA-223 is doing and how, but it also presents a challenge to any therapeutic application.” A report on the discovery is published in the Nov. 13 issue of the Proceedings of the National Academy of Sciences.

RNA is best known as a go-between that shuttles genetic information from DNA and then helps produce proteins based on that information. But, Dawson explains, a decade ago researchers unearthed a completely different class of RNA: small, nimble fragments that regulate protein production. In the case of microRNA, one member of this class, that control comes from the ability to bind to RNA messenger molecules carrying genetic information, and thus prevent them from delivering their messages. “Compared with most ways of shutting genes off, this one is very quick,” Dawson notes.

Reasoning that this quick action, along with other properties, could make microRNAs a good target for therapy development, Dawson and her team searched for microRNAs that regulate brain cells’ response to oxygen deprivation.

To do that, they looked for proteins that increased in number in cells subjected to stress, and then examined how production of these proteins was regulated. For many of them, microRNA-223 played a role, Dawson says.

In most cases, the proteins regulated by microRNA-223 turned out to be involved in detecting and responding to glutamate, a common chemical signal brain cells use to communicate with each other. A stroke or other injury can lead to a dangerous excess of glutamate in the brain, as can a range of diseases, including autism and Alzheimer’s.

Because microRNA-223 is involved in regulating so many different proteins, and because it affects glutamate receptors, which themselves are involved in many different processes, the molecule’s reach turned out to be much broader than expected, says Maged M. Harraz, Ph.D., a research associate at Hopkins who led the study. “Before this experiment, we didn’t appreciate that a single microRNA could regulate so many proteins,” he explains.

This finding suggests that microRNA-223 is unlikely to become a therapeutic target in the near future unless researchers figure out how to avoid unwanted side effects, Dawson says.

(Source: hopkinsmedicine.org)

As part of the European study TRANSEURO, five patients with Parkinson’s disease will undergo brain cell transplants at Skåne University Hospital in Lund, Sweden, in early 2013. These are the first operations of their kind in Europe for over 10 years.

The TRANSEURO study, which in Sweden is led by Lund University, is now taking a critical approach to the viability of cell therapy as a future treatment for Parkinson’s disease. Can we replace cells that die as a result of our most common neurological diseases? What are the therapies of the future for neurodegenerative diseases like Parkinson’s and Alzheimer’s?

Under the leadership of Professor of Neurology Olle Lindvall, brain researchers in Lund had already developed a method of transplanting nerve cells in the 1980s. In 1987, brain surgeon Stig Rehncrona operated on the very first patient. That study was historic and marked the first repair of the human nervous system. The news was cabled out to all the world’s media and the Swedish researchers soon graced the front page of the New York Times.

"Since the advances made in the 1980s and 1990s, the research field has encountered many obstacles. In the early 2000s, two American studies produced negative results, which meant that cell transplants for Parkinson’s disease came to a dead end," says Professor Anders Björklund, who in the 1980s was responsible for the ground-breaking discoveries in the laboratory.

Despite the unsatisfactory results presented in the American trials, cell therapy has still been seen to have effects that are entirely unique in the history of research on Parkinson’s. A third of the transplant patients have seen significant benefits of cell therapy over a very long period without medication, in some cases up to 20 years.

"For a disease with a very demanding medication regime, and for which the effects of the standard medication begin to diminish after 5 years, cell therapy represents a hope of a different life for many Parkinson’s sufferers", says Professor Håkan Widner, who is in charge of patient recruitment in Lund.

"The results of TRANSEURO will play an important role in the immediate future of cell therapy as a viable treatment. We have scrutinized the failed American studies in an attempt to optimise the technique, improve patient selection and conduct more personalised follow-up. We are hopeful that the results will be different this time", says Professor Widner.

(Source: machineslikeus.com)