Posts tagged science

Scientists at NYU Langone Medical Center have identified two genes involved in establishing the neuronal circuits required for breathing. They report their findings in a study published in the December issue of Nature Neuroscience. The discovery, featured on the journal’s cover, could help advance treatments for spinal cord injuries and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), which gradually kill neurons that control the movement of muscles needed to breathe, move, and eat.

The study identifies a molecular code that distinguishes a group of muscle-controlling nerve cells collectively known as the phrenic motor column (PMC). These cells lie about halfway up the back of the neck, just above the fourth cervical vertebra, and are “probably the most important motor neurons in your body,” says Jeremy Dasen, PhD, assistant professor of physiology and neuroscience and a member of the Howard Hughes Medical Institute, who led the three-year study with Polyxeni Philippidou, PhD, a postdoctoral fellow.

Harming the part of the spinal cord where the PMC resides can instantly shut down breathing. But relatively little is known about what distinguishes PMC neurons from neighboring neurons, and how PMC neurons develop and wire themselves to the diaphragm in the fetus.

The PMC cells relay a constant flow of electrochemical signals down their bundled axons and onto the diaphragm muscles, allowing the lungs to expand and relax in the natural rhythm of breathing. “We now have a set of molecular markers that distinguish those cells from other populations of motor neurons, so that we can study them in detail and look for ways to selectively enhance their survival,” Dr. Dasen says. Degeneration of PMC neurons is the primary cause of death in patients with ALS and spinal cord injuries.

To find out what distinguishes PMC neurons from their spinal neighbors in mice, Dr. Philippidou injected a retrograde fluorescent tracer into the phrenic nerve, which wires the PMC to the diaphragm, and then looked for the spinal neurons that lit up as the tracer worked its way back to the PMC. He used transgenic mice that express green fluorescent protein (GFP) in motor neurons and their axons in order to see the phrenic nerve. After noting the characteristic gene expression pattern of these PMC neurons, Dr. Philippidou began to determine their specific roles. Ultimately, a complicated strain of transgenic mice, based partly on mice supplied by collaborator Lucie Jeannotte, PhD, at the University of Laval in Quebec, revealed two genes, Hoxa5 and Hoxc5, as the prime controllers of proper PMC development. Hox genes (39 are expressed in humans) are well known as master gene regulators of animal development.

When Hoxa5 and Hoxc5 are silenced in embryonic motor neurons in mice, the scientists reported, the PMC fails to form its usual, tightly columnar organization and doesn’t connect correctly to the diaphragm, leaving a newborn animal unable to breathe. “Even if you delete these genes late in fetal development, the PMC neuron population drops and the phrenic nerve doesn’t form enough branches on diaphragm muscles,” Dr. Dasen says.

Dr. Dasen plans to use the findings to help understand the wider circuitry of breathing—including rhythm-generating neurons in the brain stem, which are in turn responsive to carbon dioxide levels, stress, and other environmental factors. “Now that we know something about PMC cells, we can work our way through the broader circuit, to try to figure out how all those connections are established,” he says.

"Once we understand how the respiratory network is wired we can begin to develop novel treatment options for breathing disorders such as sleep apneas," adds Dr. Philippidou.

In late October Dr. Dasen lost many of his transgenic mice when Hurricane Sandy flooded the basement of the Smilow building at NYU Langone Medical Center. But just before the hurricane hit, he sent an important group of these mice back to Dr. Jeannotte in Quebec, “so we didn’t lose everything,” he says.

(Source: eurekalert.org)

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)