Posts tagged science
Articles and news from the latest research reports.
Amputee pain linked to brain retaining picture of missing limb
Changes in the brain following amputation have been linked to pain arising from the missing limb, called ‘phantom pain’, in an Oxford University brain imaging study.
Arm amputees experiencing the most phantom limb pain were found to maintain stronger representation of the missing hand in the brain – to the point where it was indistinguishable from people with both hands.
The researchers hope their identification of brain responses correlated with the level of phantom pain can aid the development of treatment approaches, as well as increase understanding of how the brain reorganises and adapts to new situations.
The Oxford University researchers, along with Dr David Henderson-Slater of the Nuffield Orthopaedic Centre, report their findings in the journal Nature Communications.
‘Almost all people who have lost a limb have some sensation that it is still there, and it’s thought that around 80% of amputees experience some level of pain associated with the missing limb. For some the pain is so great it is hugely debilitating,’ says first author Dr Tamar Makin of the Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) at Oxford University.
Treatments for phantom limb pain tend to be limited to standard drugs for pain relief. The origin of the pain is not well understood. There may be many factors that lead to the pain, including injured nerve endings where the limb was lost and changes in the brain areas connected with the missing limb.
Lynn Ledger, a 48 year old trained therapist and advisor to charities on management training from Nottingham, took part in the study. She had her left arm amputated halfway between the elbow and shoulder in May 2009 after radiotherapy for a rare form of cancer failed to deal with an extensive tumour in her arm. She experiences severe pain as if it was coming from the missing limb.
‘I’ve pretty much tried everything to deal with the pain but nothing has worked,’ Lynn says. ‘There are no drug treatments that work because the condition is not fully understood yet. I can only use various distraction techniques, breathing exercises and mental imagery techniques, to help me manage the pain.
‘It’s very hard to describe the pain to others. I have a nonexistent limb, but I still sense it and feel pain. It’s like: imagine you are wearing a lady’s evening glove that stretches from the fingers up the arm past the elbow. But everywhere the glove covers, it’s as if it’s constantly crushing your arm. There are also shooting pains and intensely painful burning sensations that come and go, but the crushing pain is constant.
‘When I heard about this study I wanted to be involved as it was trying to improve people’s understanding of the condition.’
Kirsty Mason from Bracknell is 22 and about to start a new job as a support worker for people with mental health problems, as well as being an assessor for disabled students for their assisted technology needs. She lost her right arm four years ago just below the elbow after blacking out at a train station and falling on to the rails just ahead of a train coming in. She woke to find a wheel stopped on her arm. Since then she’s learned to write with her left hand and began driving last year. She also took part in the brain imaging study.
‘With me it’s all or nothing,’ Kirsty says of her phantom pain. ‘I get the usual pins and needles and a constant niggling pain that I can shut out by doing other things. But the worst pain is a kind of burning. It’s less frequent but it’s intense: 90-100 on the scale. It sounds silly, but the only thing I can do is stick my hand in a freezer. It numbs it.
She says: ‘I can feel my fist clenching, my fingernails digging in. I can see the hand isn’t there but the sensation is so realistic. If someone throws me a ball, I’ll move both hands to catch it. I’ll put out both hands if I fall over.’
The Oxford University team used MRI imaging to study how the phantom limb pain felt by people who have had an arm amputated is related to changes in the brain.
They compared MRI data for 18 amputees, with differing levels of phantom pain, with 11 individuals born with one hand through a limb deficiency and a control group of 22 adults with two full limbs.
The amputations had been done 18 years ago on average, but the participants still experienced sensations for the missing arm. By asking them to move the fingers of the phantom limb while in the MRI scanner, the researchers were able to look at how the missing hand is represented in the brain.
They found that the brain maintained its representation of the hand, even though the limb was no longer there. The extent to which the representation was maintained was linked to the strength and frequency of the pain the amputees felt: those feeling the greatest pain retained the strongest representation of the missing hand.
‘We were astonished to find that in amputees experiencing strong phantom pain, the brain’s response was indistinguishable from that seen in people with intact limbs,’ says Dr Makin.
The researchers found that the amount of grey matter in the phantom hand area of the brain was reduced in amputees compared to those with two hands. But again this was linked to the amount of pain amputees felt. Those experiencing stronger pain showed less structural degeneration in the missing hand area following the loss of the limb.
However, while those with strong phantom limb pain maintained the local brain structure and function for the missing hand, there was evidence that connections to other parts of the brain were disrupted more.
In particular, the representation of the missing hand was more out of synch with the area looking after the other hand on the opposite side of the brain.
Dr Makin says: ‘Most people experience “phantom” sensations in a missing limb after amputation. This disconnect between the physical world and what they are experiencing appears to be linked to a functional detachment in the brain. There seem to be reduced connections between the missing limb part of the brain and the rest of the cortex that’s involved in movement.
‘Our results may encourage rehabilitation approaches that aim to re-couple the representation of the phantom hand with the external sensory environment.’
Study reveals potential target to better treat, cure anxiety disorders
Researchers at Boston University School of Medicine (BUSM) have, for the first time, identified a specific group of cells in the brainstem whose activation during rapid eye movement (REM) sleep is critical for the regulation of emotional memory processing. The findings, published in the Journal of Neuroscience, could help lead to the development of effective behavioral and pharmacological therapies to treat anxiety disorders, such as post-traumatic stress disorder, phobias and panic attacks.
There are two main stages of sleep – REM and non-REM – and both are necessary to maintain health and to regulate multiple memory systems, including emotional memory. During non-REM sleep, the body repairs tissue, regenerates cells and improves the function of the body’s immune system. During REM sleep, the brain becomes more active and the muscles of the body become paralyzed. Additionally, dreaming generally occurs during REM sleep, as well as physiological events including saccadic eye movements and rapid fluctuations of respiration, heart rate and body temperature. One particular physiological event, which is a hallmark sign of REM sleep, is the appearance of phasic pontine waves (P-waves). The P-wave is a unique brain wave generated by the activation of a group of glutamatergic cells in a specific region within the brainstem called the pons.
Memories of fearful experiences can lead to enduring alterations in emotion and behavior and sleep plays a natural emotional regulatory role after stressful and traumatic events. Persistence of sleep disturbances, particularly of REM sleep, is predictive of developing symptoms of anxiety disorders. A core symptom of these disorders frequently reported by patients is the persistence of fear-provoking memories that they are unable to extinguish. Presently, exposure therapy, which involves controlled re-exposure to the original fearful experience, is considered one of the most effective evidence-based treatments for anxiety disorders. Exposure therapy produces a new memory, called an extinction memory, to coexist and compete with the fearful memory when the fearful cue/context is re-encountered.
The strength of the extinction memory determines the efficacy of exposure therapy. A demonstrated prerequisite for the successful development of an extinction memory is adequate sleep, particularly REM sleep, after exposure therapy. However, adequate or increased sleep alone does not universally guarantee its therapeutic efficacy.
"Given the inconsistency and unpredictability of exposure therapy, we are working to identify which process(es) during REM sleep dictate the success or failure of exposure therapy," said Subimal Datta, PhD, director and principle investigator at the Laboratory of Sleep and Cognitive Neuroscience at BUSM who served as the study’s lead author.
The researchers used contextual fear extinction training, which works to turn off the conditioned fear, to study which brain mechanisms play a role in the success of exposure therapy. The study results showed that fear extinction training increased REM sleep. Surprisingly, however, only 57 percent of subjects retained fear extinction memory, meaning that they did not experience the fear, after 24 hours. There was a tremendous increase of phasic P-wave activity among those subjects. In 43 percent of subjects, however, the wave activity was absent and they failed to retain fear extinction memory, meaning that they re-experienced fear.
"The study results provide direct evidence that the activation of phasic P-wave activity within the brainstem, in conjunction with exposure therapy, is critical for the development of long-term retention of fear extinction memory," said Datta, who also is a professor of psychiatry and neurology at BUSM. In addition, the study indicates the important role that the brainstem plays in regulating emotional memory.
Future research will explore how to activate this mechanism in order to help facilitate the development of new potential pharmacological treatments that will complement exposure therapy to better treat anxiety and other psychological disorders.
According to the National Institute of Mental Health, anxiety disorders affect approximately 40 million American adults each year. While anxiety can sometimes be a normal and beneficial reaction to stress, some people experience excessive anxiety that they are unable to control, which can negatively impact their day to day life.
(Source: eurekalert.org)
Novel storage mechanism allows command, control of memory
Introductions at a party seemingly go in one ear and out the other. However, if you meet someone two or three times during the party, you are more likely to remember his or her name. Your brain has taken a short-term memory - the introduction - and converted it into a long-term one. The molecular key to this activity is mTORC2 (mammalian target of rapamycin complex 2), according to researchers at Baylor College of Medicine in an article that appeared online in the journal Nature Neuroscience.
"Memory consolidation is a fundamental process," said Dr. Mauro Costa-Mattioli, assistant professor of neuroscience at BCM and corresponding author of the report. "Memories are at the center of our identity. They allow us to remember people, places and events for a long time, even a lifetime. Understanding the precise mechanism by which memories are stored in the brain will lead to the development of new treatments for conditions associated with memory loss".
Actin fibers
For the last five decades, neuroscientists have known that making long-lasting memories is dependent on the ability of brain cells (neurons) to synthesize new proteins. In their studies, Costa-Mattioli and his colleagues found a new mechanism by which memories are stored in the brain. The newly discovered mTORC2 regulates memory formation by modulating actin fibers, an important component of the architectural structure of the neuron.
"These actin fibers allow long-lasting changes in synaptic strength and ultimately long-term memories," said Wei Huang, a BCM graduate student and first author in the study.
Using genetically-engineered mice, the researchers found that turning off mTORC2 in the hippocampus (a crucial region required for memory formation) and surrounding areas allowed the animals to have a normal short-term memory, but prevented them from forming long-term memories. Similar to human patients with injury in the hippocampus, these mutant mice were no longer able to form new long-lasting memories.
According to Costa-Mattioli’s findings, mTORC2’s role is evolutionarily conserved and likely relevant to humans. Like mTORC2-deficient mice, fruit flies lacking TORC2 show defective long-term memory storage.
"Given that flies and mice last shared a common ancestor 500 million years ago, it is quite remarkable and telling that the function of mTORC2 in the regulation of memory is indeed maintained," said Dr. Gregg Roman, director of the Biology of Behavior Institute at the University of Houston, who contributed to the fly experiments.
Form long-term memories
The Holy Grail of memory neuroscience and to a certain extent, of industry efforts to produce a “smart drug,” has been the identification of molecules that promote the formation of long-term memory, said Costa-Mattioli. “We therefore wondered whether by turning on mTORC2 or even actin polymerization itself, we could form long-term memories more easily,” said Dr. Ping Jun Zhu, assistant professor of neuroscience at BCM, co-first author and senior scientist in Costa-Mattioli’s lab.
The team has identified a small molecule (a drug) that by activating mTORC2 and consequently actin polymerization enhances not only the synaptic strength between nerve cells but also long-term memory formation. In addition, the authors found that by directly promoting actin polymerization, with a second drug, long-term memory is generated more easily.
Costa-Mattioli’s team has identified two memory-enhancing drugs, but can they enhance memory in people? It is perhaps too early to say.
Huang said, “mTORC2, as far as we know, is really a new potential target for therapeutic treatments of human disorders. In the next few years, I predict we will see a lot of studies focusing on mTORC2 as a target.”
Memory cocktail
Costa-Mattioli’s short-term goals are to identify human cognitive disorders in which mTORC2 activity is dysfunctional and to see whether its restoration can return to normal impaired memory function in aging or even Alzheimer’s disease. But a small molecule alone might not do the job. Similar to the treatments for HIV or cancer, he believes that a combination of small molecules improving different aspects of memory formation will be required to efficiently treat cognitive disorders.
"We should start thinking about an efficient ‘memory cocktail’ rather than a single ‘memory pill.’ One molecule alone might not be enough. We may be years away from a decisive treatment, but I believe we are definitely on the right path," he said.
Others who took part in this work include Hongyi Zhou, Loredana Stoica and Mauricio Galiano, all of BCM, Krešimir Krnjević of McGill University in Montreal, Canada; and Shixing Zhang of the University of Houston.
(Image: Shutterstock)
Mental picture of others can be seen using fMRI
It is possible to tell who a person is thinking about by analyzing images of his or her brain. Our mental models of people produce unique patterns of brain activation, which can be detected using advanced imaging techniques according to a study by Cornell University neuroscientist Nathan Spreng and his colleagues.
"When we looked at our data, we were shocked that we could successfully decode who our participants were thinking about based on their brain activity," said Spreng, assistant professor of human development in Cornell’s College of Human Ecology.
Understanding and predicting the behavior of others is a key to successfully navigating the social world, yet little is known about how the brain actually models the enduring personality traits that may drive others’ behavior, the authors say. Such ability allows us to anticipate how someone will act in a situation that may not have happened before.
To learn more, the researchers asked 19 young adults to learn about the personalities of four people who differed on key personality traits. Participants were given different scenarios (i.e. sitting on a bus when an elderly person gets on and there are no seats) and asked to imagine how a specified person would respond. During the task, their brains were scanned using functional magnetic resonance imaging (fMRI), which measures brain activity by detecting changes in blood flow.
They found that different patterns of brain activity in the medial prefrontal cortex (mPFC) were associated with each of the four different personalities. In other words, which person was being imagined could be accurately identified based solely on the brain activation pattern.
The results suggest that the brain codes the personality traits of others in distinct brain regions and this information is integrated in the medial prefrontal cortex (mPFC) to produce an overall personality model used to plan social interactions, the authors say.
"Prior research has implicated the anterior mPFC in social cognition disorders such as autism and our results suggest people with such disorders may have an inability to build accurate personality models," said Spreng. "If further research bears this out, we may ultimately be able to identify specific brain activation biomarkers not only for diagnosing such diseases, but for monitoring the effects of interventions."
Human Connectome Project releases major data set on brain connectivity
The Human Connectome Project, a five-year endeavor to link brain connectivity to human behavior, has released a set of high-quality imaging and behavioral data to the scientific community. The project has two major goals: to collect vast amounts of data using advanced brain imaging methods on a large population of healthy adults, and to make the data freely available so that scientists worldwide can make further discoveries about brain circuitry.
The initial data release includes brain imaging scans plus behavioral information — individual differences in personality, cognitive capabilities, emotional characteristics and perceptual function — obtained from 68 healthy adult volunteers. Over the next several years, the number of subjects studied will increase steadily to a final target of 1,200. The initial release is an important milestone because the new data have much higher resolution in space and time than data obtained by conventional brain scans.
The Human Connectome Project (HCP) consortium is led by David C. Van Essen, PhD, Alumni Endowed Professor at Washington University School of Medicine in St. Louis, and Kamil Ugurbil, PhD, Director of the Center for Magnetic Resonance Research and the McKnight Presidential Endowed Chair Professor at the University of Minnesota.
“By making this unique data set available now, and continuing with regular data releases every quarter, the Human Connectome Project is enabling the scientific community to immediately begin exploring relationships between brain circuits and individual behavior,” says Van Essen. “The HCP will have a major impact on our understanding of the healthy adult human brain, and it will set the stage for future projects that examine changes in brain circuits underlying the wide variety of brain disorders afflicting humankind.”
The consortium includes more than 100 investigators and technical staff at 10 institutions in the United States and Europe (www.humanconnectome.org). It is funded by 16 components of the National Institutes of Health via the Blueprint for Neuroscience Research (www.neuroscienceblueprint.nih.gov).
“The high quality of the data being made available in this release reflects an intensive, multiyear effort to improve the data acquisition and analysis methods by this dedicated international team of investigators,” says Ugurbil.
The data set includes information about brain connectivity in each individual, using two distinct magnetic resonance imaging (MRI) approaches. One, called resting-state functional connectivity, is based on spontaneous fluctuations in functional MRI signals that occur in a complex pattern in space and time throughout the gray matter of the brain. Another, called diffusion imaging, provides information about the long-distance “wiring” – the anatomical pathways traversing the brain’s white matter. Each method has its own limitations, and analyses of both functional connectivity and structural connectivity in each subject should allow deeper insight than by either method alone.
Each subject is also scanned while performing a variety of tasks within the scanner, thereby providing extensive information about “Task-fMRI” brain activation patterns. Behavioral data using a variety of tests performed outside the scanner are being released along with the scan data for each subject. The subjects are drawn from families that include siblings, some of whom are twins. This will enable studies of the heritability of brain circuits.
The imaging data set released by the HCP takes up about two terabytes (2 trillion bytes) of computer memory — the equivalent of more than 400 DVDs — and is stored in a customized database called “ConnectomeDB.”
“ConnectomeDB is the next-generation neuroinformatics software for data sharing and data mining. It’s a convenient and user-friendly way for scientists to explore the available HCP data and to download data of interest for their research,” says Daniel S. Marcus, PhD, assistant professor of radiology and director of the Neuroinformatics Research Group at Washington University School of Medicine. “The Human Connectome Project represents a major advance in sharing brain imaging data in ways that will accelerate the pace of discovery about the human brain in health and disease.”
Reducing effects of traumatic events
Reducing fear and stress following a traumatic event could be as simple as providing a protein synthesis blocker to the brain, report a team of researchers from McLean Hospital, Harvard Medical School, McGill University, and Massachusetts General Hospital in a paper published in the March 4 issue of Proceedings of the National Academy of Sciences.
“This is an important basic neuroscience finding that has the potential to have clinical implications for the way individuals with posttraumatic stress disorder are treated,” said Vadim Bolshakov, PhD, director of the Cellular Neurobiology Laboratory at McLean Hospital. “We used a well-known behavioral paradigm that we think models PTSD, fear conditioning, to explore how fearful memories are formed. In our study, the level of fear exhibited by experimental subjects was significantly reduced as a result of decreased signal transfer between cells in the amygdala, a key brain region in fear-related behaviors.”
Influenced by the original findings of Karim Nader, PhD, professor of Psychology at McGill University, whose pioneering work showed that old memories should be un-stored in their brain after their recollection in order to last, Bolshakov’s team exposed rats to auditory stimulus that the animals learned to associate with a mildly traumatic event. After a single exposure to the training procedures, the rats exhibited fear during subsequent exposures to auditory stimuli. The researchers then provided the animals with rapamycin, a protein synthesis blocker, immediately after memory was retrieved in order to control bonding between the cells in the brain. The animals exhibited significantly less fear in response to the fear-invoking stimulus when retested the next day.
“The animals showed stereotypical signs of fear after the initial exposure to the auditory stimulus,” explained Nader, a co-author on the paper. “Following the administration of rapamycin, we show a significant decrease in fear, but not a complete elimination. We were surprised to note that activity between cells was significantly affected by postsynaptic mechanisms.”
The findings of this study, which was funded by a grant from the United States Department of Defense spearheaded by Roger Pitman, suggest that different plasticity rules within cells in the brain are recruited during the formation of the original fear memory and after fear memory was reactivated.
“Although further work at the molecular level needs to be completed, we are hopeful that this unexpected discovery is the foundation needed to identify ways in which we can better treat anxiety disorders in which fear condition plays a role, such as post-traumatic stress disorder,” said Bolshakov.
(Source: mcgill.ca)
A new study by Kennedy Krieger Institute’s International Center for Spinal Cord Injury (Epub ahead of print) finds that long-term lower extremity functional electrical stimulation (FES) cycling, as part of a rehabilitation regimen, is associated with substantial improvements in individuals with chronic spinal cord injury (SCI). Improvements include neurological and functional gains, as well as enhanced physical health demonstrated by decreased fat, increased muscle mass and improved lipid profile. Prior to this study’s publication in the Journal of Spinal Cord Medicine, the benefits of activity-based restorative therapy (ABRT) programs, such as FES cycling, were largely anecdotal despite publicity in conjunction with the recovery of actor and activist Christopher Reeve.
In FES, small electrical pulses are applied to paralyzed muscles to stimulate movement. In the case of FES cycling, FES pulses prompt the legs of an individual with SCI to “cycle” on an adapted stationary recumbent bicycle. The repetitive activity offers cardiovascular exercise similar to that which an able-bodied individual achieves through walking, but this new research shows that the results go far beyond basic health benefits.
“Exercise has not been commonly advocated for individuals with paralysis because of the assumption that it is of little benefit and it is challenging to exercise limbs that an individual cannot voluntarily move,” said John W. McDonald, M.D., Ph.D., senior study author and director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute. “However, we found that FES cycling is a practical form of exercise that provides substantial benefits, including improved physical integrity, enhanced neurological and functional performance, increased muscle size and strength, reduced muscle spasticity and improved quality of life.”
Mom’s Placenta Reflects Her Exposure to Stress
The mammalian placenta is more than just a filter through which nutrition and oxygen are passed from a mother to her unborn child. According to a new study by a research group from the University of Pennsylvania School of Veterinary Medicine, if a mother is exposed to stress during pregnancy, her placenta translates that experience to her fetus by altering levels of a protein that affects the developing brains of male and female offspring differently.
These findings suggest one way in which maternal-stress exposure may be linked to neurodevelopmental diseases such as autism and schizophrenia, which affect males more frequently or more severely than females.
“Most everything experienced by a woman during a pregnancy has to interact with the placenta in order to transmit to the fetus,” said Tracy L. Bale, senior author on the paper and an associate professor in the Department of Animal Biology at Penn Vet. “Now we have a marker that appears to signal to the fetus that its mother has experienced stress.”
Bale also holds an appointment in the Department of Psychiatry in Penn’s Perelman School of Medicine. Her coauthors include lead author and postdoctoral researcher Christopher L. Howerton, graduate student Christopher Morgan and former technician David B. Fischer, all of Penn Vet.
Published in the Proceedings of the National Academy of Sciences, the study builds on previous work by Bale and her colleagues which found that female mice exposed to stress during pregnancy gave birth to males who had heightened reactions to stress. Further research showed that the effect extended to the second generation: The sons of those male mice also had abnormal stress reactions.
Meanwhile, human studies conducted by other researchers have shown that males born to women who experience stress in the first trimester of pregnancy are at an increased risk of developing schizophrenia.
The Penn team hoped to find a biomarker that could account for these changes and risk factors. To be an effective signal of maternal stress, the researchers reasoned, a biomarker would need to show differences in expression between male and female offspring and would need to be different between stressed and unstressed mothers. They also wanted to find a marker that behaved similarly in humans.
Discovery opens door to new drug options for serious diseases
Researchers have discovered how oxidative stress can turn to the dark side a cellular protein that’s usually benign, and make it become a powerful, unwanted accomplice in neuronal death.
This finding, reported in Proceedings of the National Academy of Sciences, could ultimately lead to new therapeutic approaches to many of the world’s debilitating or fatal diseases.
The research explains how one form of oxidative stress called tyrosine nitration can lead to cell death. Through the common link of inflammation, this may relate to health problems ranging from heart disease to chronic pain, spinal injury, cancer, aging, and amyotrophic lateral sclerosis, or Lou Gehrig’s disease.
As part of the work, the scientists also identified a specific “chaperone” protein damaged by oxidants, which is getting activated in this spiral of cellular decline and death. This insight will provide a new approach to design therapeutic drugs.
The findings were published by scientists from the Linus Pauling Institute at Oregon State University; Maria Clara Franco and Alvaro Estevez, now at the University of Central Florida; and researchers from several other institutions. They culminate a decade of work.
“These are very exciting results and could begin a major shift in medicine,” said Joseph Beckman.
Beckman is an LPI principal investigator, distinguished professor of biochemistry, and director of the OSU Environmental Health Sciences Center. He also last year received the Discovery Award from the Medical Research Foundation of Oregon, given to the leading medical scientist in the state.
“Preventing this process of tyrosine nitration may protect against a wide range of degenerative diseases,” Beckman said. “The study shows that drugs could effectively target oxidatively damaged proteins.”
Scientists have known for decades about the general concept of oxidative damage to cells, resulting in neurodegeneration, inflammation and aging. But the latest findings prove that some molecules in a cell are thousands of times more sensitive to attack.
In this case, heat shock protein 90, or HSP90, helps monitor and chaperone as many as 200 necessary cell functions. But it can acquire a toxic function after nitration of a single tyrosine residue.
“It was difficult to believe that adding one nitro group to one protein will make it toxic enough to kill a motor neuron,” Beckman said. “But nitration of HSP90 was shown to activate a pro-inflammatory receptor called P2X7. This begins a dangerous spiral that eventually leads to the death of motor neurons.”
The very specificity of this attack, however, is part of what makes the new findings important. Drugs that could prevent or reduce oxidative attack on these most vulnerable sites in a cell might have value against a wide range of diseases.
“Most people think of things like heart disease, cancer, aging, liver disease, even the damage from spinal injury as completely different medical issues,” Beckman said. “To the extent they can often be traced back to inflammatory processes that are caused by oxidative attack and cellular damage, they can be more similar than different.
“It could be possible to develop therapies with value against many seemingly different health problems,” Beckman added.
Beckman has spent much of his career studying the causes of amyotrophic lateral sclerosis, and this study suggested the processes outlined in this study might be relevant both to that disease and spinal cord injury.
One key to this research involved new methods that allowed researchers to genetically engineer nitrotyrosine into HSP90. This allowed scientists to pin down the exact areas of damage, which may be important in the identification of drugs that could affect this process, the researchers said.
Why your brain tires when exercising
A marathon runner approaches the finishing line, but suddenly the sweaty athlete collapses to the ground. Everyone probably assumes that this is because he has expended all energy in his muscles. What few people know is that it might also be a braking mechanism in the brain which swings into effect and makes us too tired to continue. What may be occurring is what is referred to as ‘central fatigue’.
"Our discovery is helping to shed light on the paradox which has long been the subject of discussion by researchers. We have always known that the neurotransmitter serotonin is released when you exercise, and indeed, it helps us to keep going. However, the answer to what role the substance plays in relation to the fact that we also feel so exhausted we have to stop has been eluding us for years. We can now see it is actually a surplus of serotonin that triggers a braking mechanism in the brain. In other words, serotonin functions as an accelerator but also as a brake when the strain becomes excessive," says Associate Professor Jean-François Perrier from the Department of Neuroscience and Pharmacology, who has spearheaded the new research.
Help in the battle against doping
Jean-François Perrier hopes that mapping the mechanism that prompts central fatigue will be useful in several ways. Central fatigue is a phenomenon which has been known for about 80 years; it is a sort of tiredness which, instead of affecting the muscles, hits the brain and nervous system. By conducting scientific experiments, it is possible to observe and measure that the brain sends insufficient signals to the muscles to keep going, which in turn means that we are unable to keep performing. This makes the mechanism behind central fatigue an interesting area in the battle against doping, and it is for this reason that Anti Doping Danmark has also helped fund the group’s research.
"In combating the use of doping, it is crucial to identify which methods athletes can use to prevent central fatigue and thereby continue to perform beyond what is naturally possible. And the best way of doing so is to understand the underlying mechanism," says Jean-François Perrier.
Developing better drugs
The brain communicates with our muscles using so-called motoneurons. In several diseases, motoneurons are hyperactive. This is true, for example, of people suffering from spasticity and cerebral palsy, who are unable to control their movements. Jean-François Perrier therefore hopes that, in the long term, this new knowledge can also be used to help develop drugs against these symptoms and to find out more about the effects of antidepressants.
"This new discovery brings us a step closer to finding ways of controlling serotonin. In other words, whether it will have an activating effect or trigger central fatigue. It is all about selectively activating the receptors which serotonin attaches to," explains Jean-François Perrier.
"For selective serotonin re-uptake inhibitor (SSRI) drugs which are used as antidepressants, we can possibly help explain why those who take the drugs often feel more tired and also become slightly clumsier than other people. What we now know can help us develop better drugs," concludes Jean-François Perrier.