Brain and Body – Writing Science News

Brain shock therapy that actually works!

Justin Williams ’13

Just today, April 18th, 2010, researchers from various universities (University of Pennsylvania School of Medicine, Tufts University, and The University of Illinois in Urbana-Champaign) published that they have developed a new and improved way to implant electrodes into the brain in order to monitor and react to different patterns of brain activity.

As of now, the most advanced methods we have for measuring brain activity are either thin needle-like electrodes that can be inserted deep within the brain or micro-electrode arrays (made up on dozens of electrodes attached to a silicon base or grid). Although both of these methods are useful, they each have drawbacks. The needle-like electrodes are very vulnerable and can be moved or broken when the brain changes position and the silicon base of the micro-electrode arrays do not allow for much flexibility when attaching to the surface of the brain.

21719 — An example of an electrode array set up on a model of the brains surface.

However, now researcher Dr. Brian Litt M.D. from University of Pennsylvania School of Medicine and colleagues have developed a new and improved method that uses a silk base instead of silicon. Dr. Litt, when explaining their reasoning behind their micro-electrode array design, said that “the implants contain metal electrodes that are 500 microns thick, or about five times the thickness of a human hair. The absence of sharp electrodes and rigid surfaces should improve safety, with less damage to brain tissue. Also, the implants’ ability to mold to the brain’s surface could provide better stability; the brain sometimes shifts in the skull and the implant could move with it. Finally, by spreading across the brain, the implants have the potential to capture the activity of large networks of brain cells.” In addition to these advantages, the silk base can also be dissolved at a controlled time point which would provide for even better stability for the electrodes.

The potential impact of this new method for measuring and altering brain activity is enormous.This design has promising implications for treatment of epilepsy, spinal cord injuries, and other neurological disorders. For example, the arrays could be read the start of epileptic activity and deliver a shock that would calm the brain down and prevent the seizure. Although these results are a step in the right direction, researchers are still experimenting with varying numbers and arrangements of arrays in order to maximize the clarity of the measurements the electrodes read.

Sources:

http://www.eurekalert.org/pub_releases/2010-04/nion-abd041610.php

http://www.nature.com/nmat/journal/vaop/ncurrent/full/nmat2745.html

Sleepy Soldiers’ Split-Second Situation Assessment Skewed

Study demonstrates decrease in ability to make rapid judgement calls due to sleep deprivation.

By: Nicole Myers

In a study conducted at the University of Texas and published in the journal Sleep, researchers found that sleep deprivation negatively impacts information-integration, the type of cognitive processing that allows fast, accurate, gut-feeling decisions.

Soldiers in combat rely heavily on the ability to instantly make the right decisions in high pressure situations. Researcher Tom Maddox explains, “information-integration… is critical in situations when solders need to make split-second decisions about whether a potential target is an enemy soldier, a civilian, or one of their own.” Unfortunately, combat missions don’t exactly lend themselves to full nights of sleep, and soldiers in these operations are often extremely sleep- deprived.

The study tested 49 West Point Cadets on information-integration tasks, once as a baseline and then again after 24 hours of either sleep deprivation or a normal sleep-wake cycle. While the rested cadets significantly improved their scores in the second round of testing, the sleep-deprived cadets’ scores dropped slightly. This indicates that even the mild sleep-deprivation of one night’s sleep loss impacted the cadets’ ability to use this crucial form of decision making.

Researchers observed that one way sleep-deprivation impaired decision making was by causing subjects to shift from the fast and accurate cognitive strategy of information integration to a slower, more controlled, but less-effective rule-based approach, in which they tended to over-think the problems.

The effect that sleep-deprivation had on decision making varied among individuals. Those who had a tendency to use a rule-based approach to problem solving in the first place were more vulnerable to the effects of sleep-deprivation. Some subjects continued to use an information-integration approach despite sleep-deprivation, and their performance showed no decline in the second set of testing. This suggests that the cognitive function necessary for information-integration strategies is not necessarily strongly affected by sleep deprivation. But, the use of an information-integration strategy in a task may require active inhibition of rule-based strategies, and this inhibitory process is what is vulnerable to the effects of sleep deprivation.

An understanding of the effects of sleep-deprivation on various cognitive functions and decision making abilities is critical for a military in a time of war, when enormous physical demands are placed on soldiers who are often deprived of sleep and sustenance and who must make split-second life or death decisions.

For the original research click: http://www.journalsleep.org/ViewAbstract.aspx?pid=27617

Change Your Mind: How Stress Reshapes Your Brain

By Kelly Lohr

It has been known for a while that too much stress can be bad for your health. A new study now shows that it can affect your brain too. Research through a collaboration between Rockefeller University and Cornell University suggests that stress can been linked to harmful changes in some brain structures. Sometimes these brain changes can be advantageous, such as making new synaptic connections to remember and learn from a stressful, life-threatening event. However, some changes can be detrimental.

g001098 — A mouse hippocampus labeled with NeuroTrace® green fluorescent Nissl stain

The project has identified a protein possibly involved in remodeling the brain under stress. It was found that the brains of mice lacking the protein called brain-derived neurotrophic factor (BDNF) look like the brains of stressed mice. The study examined changes in the neurons of the hippocampus, a brain area important in memory, mood, and cognition. When normal mice were stressed through confinement to a small space, the tiny projections on their neurons called dendrites retracted in the hippocampus. The hippocampus itself was also reduced in overall volume. The study compared these mice to other mice that were missing a copy of the gene that produces BDNF. It was found that these genetically-altered mice had brains resembling those of stressed mice.

Not only does this finding show that stress can produce brain changes. Bruce McEwan of Rockefeller University suggested that BDNF also may be “one of the proteins that play a role in mediating the brain’s plasticity.” This holds promise for a better understanding of the role of neuronal remodeling in the hippocampus and its importance in memory and emotion.

Written April 13, 2010

For more information, visit http://www3.interscience.wiley.com/journal/123249229/abstract?CRETRY=1&SRETRY=0.

Could we re-grow lost limbs?

Researchers discover gene deletion that allows tissue regeneration in mammals.

By: Nicole M. Myers

Mar. 2010- Researchers at the Wistar Institute, a international leader in biomedical research, have discovered a gene that could regulate regeneration in mammals, bringing the possibility of re-growing amputated extremities one step closer to reality. The lab identified a gene called p21, that when turned off confers to mice the ability to regenerate lost tissue.

The ability to regenerate lost appendages is common but sporadically observed in nature, as in animals such as flatworms, sponges, and salamanders, but the phenomenon was previously unknown in mammals. Mammals are capable of replacing some types of tissue, such as liver lobes, damaged skeletal muscle cells, epithelium, the gut lining, and even brain cells to some extent. Typically though, the mammalian healing process involves the formation of scar tissue, rather than new cells. Animals like salamanders begin healing with the formation of a blastema, a structure that allows cells to rapidly proliferate and differentiate as embryonic stem cells do, until the appendage is replaced without scarring.

This research began with a chance observation in a particular strain of laboratory mice, known as MRL mice. Researchers used the standard technique of piercing holes in the mice’s ears for identification. However, within a couple weeks, the holes had unexpectedly closed without a trace. The researchers then began to investigate the genetics of the MRL mice to see what might be behind their unique healing ability, and they found that the p21 gene was inactivated. Further research indicated that mice lacking the p21 gene were able to completely regenerate lost or damaged tissue without forming a scar, re-grow cartilage, and partially regenerate amputated digits.

The p21 gene is a cell cycle regulator that blocks the cell cycle progression when there is damage to the DNA, preventing the cells from dividing and potentially becoming cancerous. Similar to naturally regenerative creatures, mice that lack p21 show an increase in DNA damage, but also an increase in apoptosis, or the programmed death of impaired cells. Researchers suggest that “The combined effects of an increase in highly regenerative cells and apoptosis may allow the cells of these organisms to divide rapidly without getting out of control and becoming cancerous.”

Amputation injuries are some of the most devastating and debilitating wounds soldiers sustain in combat. According to the Army Office of the Surgeon General, between September 2001 and January 2009, 1,286 soldiers suffered amputation injuries in Operation Iraqi Freedom and Operation Enduring Freedom. This is the first research to succeed in this degree of tissue regeneration in mammals, giving hope that someday, we may have the ability to restore these lost limbs.

To read the original research published in Proceedings of the National Academy of Science, click: http://www.pnas.org/content/107/13/5845.full

A Fungus with a Deadly Sweet Tooth

By: Kristen Kocher

This is your brain on Cryptococcus — severe brain swelling caused by a Cryptococcal infection

As it turns out, humans aren’t the only ones with a sweet tooth. According to an article published last week (April 5, 2010) in mBio online microbiology journal, a certain species of fungus, Cryptococcus, were found to thrive and reproduce through consumption of a sugar, inositol, which is commonly found in the human brain and spinal cord.

Joseph Heitman, M.D. and Ph.D. and his team of researchers who have been studying Cryptococcus at the Duke Department of Molecular Research believe they have identified a set of almost a dozen genes that code for sugar transport molecules. Sugar transport molecules are important in borrowing sugars from parts of the body to use where they are needed. Normal fungi have only two genes that code for these sugar transport molecules. It is therefore hypothesized that because of the increased number of genes coding for sugar transport molecules in Cryptococcus, this fungus is able to more quickly gather sugars to consume. According to Heitman, “Inositol is abundant in the human brain and in the fluid that bathes it (cerebral spinal fluid), which may be why this fungus has a predilection to infect the brain and cause meningitis. It has the machinery to efficiently move sugar molecules inside of its cells and thrive.” Meningitis is a serious health problem that involves the swelling of the area around the brain, causing a build up of fluid, which can have negative effects on brain function. Meningitis is a medical emergency because it occurs quickly and often results in permanent brain damage or death.

Before it was able to infect the brain, it is believed that Cryptococcus originally localized itself on plants. Plants are rich in inositol and most likely caused Cryptococcus to adapt and change its genome to produce more sugar transport molecules in order to survive and replicate. Because the brain and spinal cord naturally have very high concentrations of inositol it makes sense that Cryptococcus would target the brain as a niche.

Furthermore, it has been found that inositol stimulates sexual reproduction in Cryptococcus, so in areas of plentiful inositol concentrations, such as the brain, reproduction occurs often and rapidly.

Chaoyang Xue, Ph.D., formerly a postdoctoral research associate in the Heitman lab and now an assistant professor at the Public Health Research Institute at the University of Medicine and Dentistry of New Jersey, comments, “A connection between the high concentration of free inositol and fungal infection in the human brain is suggested by our studies. Establishing such a connection could open up a new way to control this deadly fungus.”

While Cryptococcus’ love for sugar may seem only beneficial, it turns out that because the fungus relies so heavily on inositol for nutrition, scientists have found a way to essentially put the fungus on an “Atkin’s-esque low-carb diet”. This “diet” would greatly reduce the ability of Cryptococcus to multiply, thus lessening its effects on the human brain.

Original Press Release

Check out mBio online microbiology journal for more articles and other information on this research.

Click here information on the Heitman lab

Nano probes: the future of drug delivery?

by Johnathan Nieves ’11

Scientists have developed an extremely small probing device that is capable of binding to a cells surface and eavesdropping on its internal electrical activity. This may help to provide insight into how cells communicate and how they respond to medication delivered through the probe.

Ever think we could spy on a cell? We have been able to for almost thirty years now, but a new technique is purported to no do it substantially better. Stanford Researchers recently (March 30) published a paper describing their success in developing a nanometer-scale probe capable of binding and becoming a part of a single cell’s membrane. The paper, published in Proceedings of the National Academy of Science, offers insight into the ability for researchers to eavesdrop on the inner electrical activity of individual cells. The use of the nano probe as a conduit for inserting medication into a cell’s interior is also being cited by the Stanford researchers.

The study, spearheaded by Nick Melosh and Benjamin Almquist, focused on designing a probe in a way that allowed it to mimic a component of the cell membrane. The cell membrane, or cell wall, is the outermost encapsulating structure of a cell that protects it from the outside environment. The key to the probe’s easy insertion and the great affinity it has for the cell membrane is due to its engineering. The probe was engineered in a way that allowed it to mimic a type of cell membrane gatekeeper protein – a molecule naturally found in the cell membrane that regulates what enters and exits the cell.

Image depicting the nano-probe binding to the cell membrane. (Credit: Benjamin Almquist, Stanford University)

“What we have done is make an inorganic version of one of those membrane proteins, which sits in the membrane without disrupting it,” said Melosh. “The probes fuse into the membranes spontaneously and form good, strong junctions there.” The attachment is so strong, “we cannot pull them out. The membrane will just keep deforming rather than let go of the probes.” The 600-nanometer-long probe has integrated so well into membranes that the researchers have dubbed it the “stealth” probe.

Current methods involved in cell probing are limited in that they only allow access to the cell for few hours. Additionally, the methods are extremely destructive and damaging to cells. Melosh and Almquist are the first to implant a cell probe with very little damage to the cell.

Up to now, poking a hole in a cell membrane has largely relied on brute force, Melosh said. “We can basically rip holes in the cells using suction, we can use high voltage to puncture holes in their membranes, both of which are fairly destructive […]; many of the cells don’t survive.” That limits the duration of any observations, particularly electrical measurements of cell function.

“Ideally, what you’d like to be able to do is have an access port through the cell membrane that you can put things in or take things out, measure electrical currents … basically full control,” commented Melosh. “That’s really what we’ve shown – this is a platform upon which you can start building those kinds of devices.”

Melosh and Almquist are currently working with human red blood cells, cervical and ovary cancer cells to demonstrate the functionality of the probes in living cells.

To view the press release pertaining to this article, click here.

No Time to Exercise? Think Again

By Abby Larson

Not having enough time is no longer an excuse to avoid exercising. Scientists at McMaster University in Canada published a study in The Journal of Physiology on short term high-intensity interval training (HIT), which consists of a series of short bursts of intense exercise with short recovery breaks in between. They found that HIT works as well in building muscle and improving oxygen delivery to muscles as long term exercise.

The study, headed by Professor Martin Gibala, was performed on college students on a stationary bike with a workload at about 95% maximum heart rate. Gibala found that doing 10 one-minute sprints on the stationary bike with one minute of rest in between resulted in the same physical benefits as long duration endurance biking. This means that the muscular benefits of exercise can be achieved with less time and less exercise. However, long-term exercise is still necessary for weight loss to maximize calories burned, but short-term, high intensity exercise is far more beneficial that no exercise at all.

The reasons behind these results are not yet known, but Gibala found that HIT activates some of the cellular pathways that are associated with producing the health benefits from endurance training.

These findings are not just for athletes trying to get into shape. The scientists at McMaster think that a less “all-out” HIT method can be beneficial for people who require the benefits of exercise but are not advised to exercise for prolonged periods of time. The team’s future research will examine the effects of HIT on the elderly, obese, and people with metabolic diseases such as diabetes.

So next time you only have 10-20 minutes to exercise, hop on a stationary bike to try this time-efficient and effective form of exercise. Remember, though, that exercise plans should be catered towards an individual’s fitness goals.

Time to Get Paranoid about your Thyroid

By: Shelly Hwang

April 3, 2010

Most young adults from the ages of 18 to 44 don’t give much thought to their thyroid, but a study published earlier this month in Stroke: Journal of the American Heart Association reveals increased risk of stroke in young adults with an overactive thyroid.

So what exactly is an overactive thyroid? Hyperthyroidism, or an overactive thyroid, is a condition that causes overproduction of thyroid hormone, which increases metabolism and causes sweating, diarrhea, weight loss, and nervousness. Hyperthyroidism is common, affecting about 0.5-2% of the worldwide population, particularly young adults. The study shows an association between hyperthyroidism and ischemic stroke, which is the most common type of stroke caused by blocked arteries in or leading to the brain.

The study compared data on 3,176 young adults diagnosed with hyperthyroidism between January 1998 and December 2001 and 25,408 patients without thyroid disease, with the average age being 32 years. After five years, 198 of the 28,584 patients developed ischemic stroke (0.7%), with 1% of the hyperthyroidism patients and 0.6% of the comparison group having a stroke. After accounting for many factors such as age, gender, high blood pressure, diabetes, and an irregular heart rhythm called atrial fibrillation (AF), the risk of hyperthyroidism patients having a stroke was 44 percent higher than those without hyperthyroidism.

In adults over the age of 60, Hyperthyroidism is known to be associated with AF, which occurs when the heart beats irregularly and ineffectively and can lead to a stroke. However, the risk of stroke in younger people with hyperthyroidism has not been previously studied. This study could lead to a new screening process for young adults to help lower risk of developing a stroke sooner than expected.

Press Release

American Stroke Association

Live long and prosper

Justin Williams ’13

On April 1, 2010, scientists funded by the Biotechnology and Biological Sciences Research Council at the University of Birmingham uncovered a gene that is strongly related to the lifespan in Caenorhabditis elegans (C. elegans) and three of its close relatives. Scientists used longevity of life, immunity, and resistance to stress as the main determinants of the worms lifespan.

429149a-f2.2 — Activation of DAF-16 gene promoting increased resistance to stress.

Head researcher Dr. Robin May explains the purpose of their research: “We wanted to find out how normal ageing is being governed by genes and what effect these genes have on other traits, such as immunity.” To do this, they looked at a gene that has been known to play an important role in the ‘dauer’ stage of development and influence the longevity of life in worms, gene DAF-16.

To figure out the exact role this gene plays in the worms lifespan, researchers sought out the relationship between the worms lifespan/resistance to stress and that its expression of the DAF-16 gene. To induce stress in worms scientists exposed “them to high temperature, heavy metals and a range of bacterial and fungal diseases.”

Their results were very promising. As they expected, the DAF-16 gene and it’s expression in worms positively correlated to their lifespan, and, in general, “higher levels of DAF-16 activity correlated with longer life, increased stress resistance and better immunity against some infections.”

Although this study was performed on worms, scientists have high expectations for the implications in humans. Researchers say that “it is possible that this knowledge could open up new avenues for altering ageing, immunity and resistance to stresses in humans.”

Sources:

http://www.bbsrc.ac.uk/media/releases/2010/100401-ageing-gene-found-to-govern-lifespan.aspx

http://www.ncbi.nlm.nih.gov/pubmed/12845331

History of Smoking Reduces Risk of Parkinson’s Disease

By Kelly Lohr

Believe it or not, a new study has shown that a history of cigarette smoking may actually benefit your health. Over the last decade, Honglei Chen led a study out of the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina examining long-term health effects of the habit. Over 300,000 AARP members between the ages of 50 to 71 were surveyed about lifestyle choices over a ten-year period. Of these subjects, 0.05% of the individuals developed Parkinson’s disease.

Parkinson’s disease is a neurodegenerative disorder characterized by the breakdown of cells which release the neurotransmitter dopamine in a brain area known as the substantia nigra. Typical symptoms of Parkinson’s include uncontrollable muscle movements, poor posture, and rigidity. Of the participants from Chen’s study, it was found that current smokers reduced their risk of Parkinson’s disease by 44% as compared to non-smokers. Previous smokers who had quit reduced their risk of Parkinson’s by 22%.

Interestingly, the risk of developing Parkinson’s disease did not change based on how many cigarettes a person smoked per day. Instead, the length of the history of smoking was correlated to reduction in disease risk. Those who smoked for at least 40 years were 46% less likely to develop Parkinson’s, whereas those who smoked between 30 and 39 years reduced their risk by 35%. However, individuals who smoked for nine years or less only reduced their risk by 8%.

Despite Chen’s findings, smoking does not slow the progression of Parkinson’s once it develops. For this reason, experts do not suggest that nicotine or other chemicals in cigarettes should be considered as effective Parkinson’s disease treatments. Despite this, an improved understanding of the mechanisms behind the reduced risk may lead to breakthroughs in the causes of the disease.

For more information, visit http://www.neurology.org/cgi/content/abstract/74/11/878.