Posts tagged science
Articles and news from the latest research reports.
New drug could treat Alzheimer’s, multiple sclerosis and brain injury
July 24, 2012
A new class of drug developed at Northwestern University Feinberg School of Medicine shows early promise of being a one-size-fits-all therapy for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and traumatic brain injury by reducing inflammation in the brain.
Northwestern has recently been issued patents to cover this new drug class and has licensed the commercial development to a biotech company that has recently completed the first human Phase 1 clinical trial for the drug.
The drugs in this class target a particular type of brain inflammation, which is a common denominator in these neurological diseases and in traumatic brain injury and stroke. This brain inflammation, also called neuroinflammation, is increasingly believed to play a major role in the progressive damage characteristic of these chronic diseases and brain injuries.
By addressing brain inflammation, the new class of drugs — represented by MW151 and MW189 — offers an entirely different therapeutic approach to Alzheimer’s than current ones being tested to prevent the development of beta amyloid plaques in the brain. The plaques are an indicator of the disease but not a proven cause.
A new preclinical study published today in the Journal of Neuroscience, reports that when one of the new Northwestern drugs is given to a mouse genetically engineered to develop Alzheimer’s, it prevents the development of the full-blown disease. The study, from Northwestern’s Feinberg School and the University of Kentucky, identifies the optimal therapeutic time window for administering the drug, which is taken orally and easily crosses the blood-brain barrier.
"This could become part of a collection of drugs you could use to prevent the development of Alzheimer’s," said D. Martin Watterson, a professor of molecular pharmacology and biological chemistry at the Feinberg School, whose lab developed the drug. He is a coauthor of the study.
In previous animal studies, the same drug reduced the neurological damage caused by closed-head traumatic brain injury and inhibited the development of a multiple sclerosis-like disease. In these diseases as well as in Alzheimer’s, the studies show the therapy time window is critical.
How a Single Brain Trauma May Lead to Alzheimer’s Disease
ScienceDaily (July 24, 2012) — A study, performed in mice and utilizing post-mortem samples of brains from patients with Alzheimer’s disease, found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate an enzyme associated with Alzheimer’s. The paper, published in The Journal of Neuroscience, identifies the complex mechanisms that result in a rapid and robust post-injury elevation of the enzyme, BACE1, in the brain. These results may lead to the development of a drug treatment that targets this mechanism to slow the progression of Alzheimer’s disease.
"A moderate-to-severe TBI, or head trauma, is one of the strongest environmental risk factors for Alzheimer’s disease. A serious TBI can lead to a dysfunction in the regulation of the enzyme BACE1. Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer’s disease," said first author Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM).
Building on her previous work, neuroscientist Giuseppina Tesco, MD, PhD, of Tufts University School of Medicine (TUSM), led a research team that first used an in vivo model to determine how a single episode of TBI could alter the brain. In the acute phase (first two days) following injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and an elevation of BACE1 enzyme level was observed.
Next, in an analysis of post-mortem brain samples from patients with Alzheimer’s disease, the researchers found that GGA1 and GGA3 levels were reduced while BACE1 levels were elevated in the brains of Alzheimer’s disease patients compared to the brains of people without Alzheimer’s disease, suggesting a possible inverse association.
In an additional experiment using a mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer’s disease patients, the team found that one week following traumatic brain injury, BACE1 and amyloid-beta levels remained elevated even when GGA1 levels had returned to normal. The research suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed in the sub-acute phase, or seven days, after injury.
"When the proteins are at normal levels, they work as a clean-up crew for the brain by regulating the removal of BACE1 enzymes and facilitating their transport to lysosomes within brain cells, an area of the cell that breaks down and removes excess cellular material. BACE1 enzyme levels may be stabilized when levels of the two proteins are low, likely caused by an interruption in the natural disposal process of the enzyme," said Tesco, assistant professor of neuroscience at Tufts School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.
"We found that GGA1 and GGA3 act synergistically to regulate BACE1 post-injury. The identification of this interaction may provide a drug target to therapeutically regulate the BACE1 enzyme and reduce the deposition of amyloid-beta in Alzheimer’s patients," she continued. "Our next steps are to confirm these findings in post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries."
Moderate-to-severe TBIs are caused most often by traumas, such as severe falls or motor vehicle accidents, that result in a loss of consciousness. Not all traumas to the head result in a TBI. According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a TBI. Concussions, the mildest form of a TBI, account for about 75% of all TBIs. Studies have linked repeated head trauma to brain disease and some previous studies have linked single events of brain trauma to brain disease, such as Alzheimer’s. Alzheimer’s disease currently affects as many as 5.1 million Americans and is the most common cause of dementia in adults age 65 and over.
Source: Science Daily
Brain discovery sheds light on link between vision and emotion
Neuroscientists have discovered a new area of the brain that is uniquely specialised for peripheral vision and could be targeted in future treatments for panic disorders and Alzheimer’s disease.
Published today in high impact journal Current Biology, researchers led by Dr Hsin-Hao Yu and Professor Marcello Rosa from Monash University’s Department of Physiology found that a brain area, known as prostriata, was specialised in detecting fast-moving objects in peripheral vision.
This area, located in a primitive part of the cerebral cortex, has characteristics unlike any other visual area described before, including a “direct line” of communication to brain areas controlling emotion and quick reactions.
Dr Yu said the discovery, identified during the development of the Monash Vision Group’s bionic eye, funded through the ARC Research in Bionic Vision Science and Technology Initiative, could lead to new treatments for panic disorders such as agoraphobia (fear of open spaces) and may extend into other medical areas including Alzheimer’s treatment.
“The brain is the most complex organ in the human body and perhaps the most remarkable. These findings change how we think of the brain in terms of how visual information is processed,” Dr Yu said.
“This area is likely to be hyperactive in panic disorder, with agoraphobia. This knowledge could lead to treatment options for the hyperactivity, and therefore sensitivity to such disorders, particularly the fear of open spaces.
“Correlation with previous studies also shows that prostriata is one of the first areas affected in Alzheimer’s disease. This knowledge helps to explain spatial disorientation and the tendency to fall, which are among the earliest signs of a problem associated with Alzheimer’s.”
Professor Rosa said this area had ultra-fast responses to visual stimuli, simultaneously broadcasting information to brain areas that control attention, emotional and motor reactions. This challenges current conceptions of how the brain processes visual information.
“This suggests a specialised brain circuit through which stimuli in peripheral vision can be fast-tracked to command quickly coordinated physical and emotional responses,” Professor Rosa said.
Chronic pain distorts sufferers’ sense of space and time
July 24, 2012
Einstein’s famous theory of relativity proposed that matter can distort space and time. Now a new study recently published in the journal Neurology suggests that chronic pain can have the same effect.
Neuroscientists from the University of South Australia, Neuroscience Research Australia and the University of Milano Bicocca in Italy, studied people with chronic back pain, the most common painful condition which costs western countries billions of dollars in lost productivity every year.
They presented identical vibration stimuli to the painful area and a non-painful area and noted that the stimuli were processed more slowly by the brain if they came from the painful area.
The most striking finding, however, was that the same effect occurred if the stimuli were delivered to a healthy body part being held near the painful area.
Lead author of the study, Professor Lorimer Moseley from the University of South Australia, says it was not altogether surprising that, in people with chronic pain, there are changes in the way the brain processes information from and about the painful body part.
“But what is remarkable is that the problem affects the space around the body as well as the body itself,” Prof Moseley says.
Experiments showed that if a hand was held near the painful area of the back, the brain would almost ‘neglect’ that hand.
“The potential similarity between our findings and the time-space distortion predicted by the relativity theory is definitely intriguing,” Prof Moseley says.
“Obviously, here it is not external space that is distorted but the ability of the brain to represent that space within its neural circuitry.
“This finding opens up a whole new area of research into the way the brain allows us to interact with the world and how this can be disrupted in chronic pain.”
Provided by University of South Australia
Source: medicalxpress.com
HCN2 ion channels: an emerging role as the pacemakers of pain
Acute nociceptive pain is caused by the direct action of a noxious stimulus on pain-sensitive nerve endings, whereas inflammatory pain (both acute and chronic) arises from the actions of a wide range of inflammatory mediators released following tissue injury. Neuropathic pain, which is triggered by nerve damage, is often considered to be very different in its origins, and is particularly difficult to treat effectively. Here we review recent evidence showing that members of the hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channel family – better known for their role in the pacemaker potential of the heart – play important roles in both inflammatory and neuropathic pain. Deletion of the HCN2 isoform from nociceptive neurons abolishes heat-evoked inflammatory pain and all aspects of neuropathic pain, but acute pain sensation is unaffected. This work shows that inflammatory and neuropathic pain have much in common, and suggests that selective blockers of HCN2 may have value as analgesics in the treatment of pain.
Better Understanding of Memory Retrieval Between Children and Adults
ScienceDaily (July 24, 2012) — Neuroscientists from Wayne State University and the Massachusetts Institute of Technology (MIT) are taking a deeper look into how the brain mechanisms for memory retrieval differ between adults and children. While the memory systems are the same in many ways, the researchers have learned that crucial functions with relevance to learning and education differ.
The team’s findings were published on July 17, 2012, in the Journal of Neuroscience.
According to lead author Noa Ofen, Ph.D., assistant professor in WSU’s Institute of Gerontology and Department of Pediatrics, cognitive ability, including the ability to learn and remember new information, dramatically changes between childhood and adulthood. This ability parallels with dramatic changes that occur in the structure and function of the brain during these periods.
In the study, “The Development of Brain Systems Associated with Successful Memory Retrieval of Scenes,” Ofen and her collaborative team tested the development of neural underpinnings of memory from childhood to young adulthood. The team of researchers exposed participants to pictures of scenes and then showed them the same scenes mixed with new ones and asked them to judge whether each picture was presented earlier. Participants made retrieval judgments while researchers collected images of their brains with magnetic resonance imaging (MRI).
Using this method, the researchers were able to see how the brain remembers. “Our results suggest that cortical regions related to attentional or strategic control show the greatest developmental changes for memory retrieval,” said Ofen.
The researchers said that older participants used the cortical regions more than younger participants when correctly retrieving past experiences.
"We were interested to see whether there are changes in the connectivity of regions in the brain that support memory retrieval," Ofen added. "We found changes in connectivity of memory-related regions. In particular, the developmental change in connectivity between regions was profound even without a developmental change in the recruitment of those regions, suggesting that functional brain connectivity is an important aspect of developmental changes in the brain."
This study marks the first time that the development of connectivity within memory systems in the brain has been tested, and the results suggest that the brain continues to rearrange connections to achieve adult-like performance during development.
Ofen and her research team plan to continue research in this area, focused on modeling brain network connectivity, and applying these methods to study abnormal brain development.
Source: Science Daily
Mice have system to handle smell of fear
July 23, 2012
Mice appear to have a specialized system for detecting and at least initially processing instinctually important smells such as those that denote predators. The finding raises a question about whether their response to those smells is hardwired.
A separate subsystem for the smell of fear. Experiments in mice suggest neurons that detect odors associated with an instinctive response — like fleeing when an approaching predator is detected — are configured differently than other olfactory neurons. Further research could determine whether this system automatically triggers flight or other primal behaviors.Credit: Mike Cohea/Brown University
PROVIDENCE, R.I. [Brown University] — A new study finds that mice have a distinct neural subsystem that links the nose to the brain and is associated with instinctually important smells such as those emitted by predators. That insight, published online this week in Proceedings of the National Academy of Sciences, prompts the question whether mice and other mammals have specially hardwired neural circuitry to trigger instinctive behavior in response to certain smells.
In the series of experiments and observations described in the paper, the authors found that nerve cells in the nose that express members of the gene family of trace amine-associated receptors (TAAR) have several key biological differences from the much more common and diverse neurons that express members of the olfactory receptor gene family. Those other nerve cells detect a much broader range of smells, said corresponding author Gilad Barnea, the Robert and Nancy Carney Assistant Professor of Neuroscience at Brown University.
The differences between TAAR neurons and olfactory receptor neurons led Barnea and his co-authors to conclude that they form an independent subsystem for certain smells.
“Our observations suggest that the TAAR-expressing sensory neurons constitute a distinct olfactory subsystem that extracts specific environmental cues that then elicit innate responses,” Barnea said.
Strobe Eyewear Training Improves Visual Memory
ScienceDaily (July 23, 2012) — Stroboscopic training, performing a physical activity while using eyewear that simulates a strobe-like experience, has been found to increase visual short-term memory retention, and the effects lasted 24 hours.
(Credit: Image courtesy of Duke University)
Participants completed a memory test that required them to note the identity of eight letters of the alphabet that were briefly displayed on a computer screen. After a variable delay, participants were asked to recall one of the eight letters. On easy-level trials, the recall prompt came immediately after the letters disappeared, but on more difficult trials, the prompt came as late as 2.5 seconds following the display. Because participants did not know which letter they would be asked to recall, they had to retain all of the items in memory.
"Humans have a memory buffer in their brain that keeps information alive for a certain short-lived period," said Greg Appelbaum, assistant professor of psychiatry at Duke University and first author of the study. "Wearing the strobe eyewear during the physical training seemed to boost the ability to retain information in this buffer."
The strobe eyewear disrupts vision by only allowing the user to see glimpses of the world. The user must adjust their visual processing in order to perform normally, and this adjustment produces a lingering benefit; once participants removed the strobe eyewear, there was an observed boost in their visual memory retention, which was found to last 24 hours.
Earlier work by Appelbaum and the project’s senior researcher, Stephen Mitroff, had shown that stroboscopic training improves visual perception, including the ability to detect subtle motion cues and the processing of briefly presented visual information. Yet the earlier study had not determined how long the benefits might last.
"Our earlier work on stroboscopic training showed that it can improve perceptual abilities, but we don’t know exactly how," says Mitroff, associate professor of psychology & neuroscience and member of the Duke Institute for Brain Sciences. "This project takes a big step by showing that these improved perceptual abilities are driven, at least in part, by improvements in visual memory."
"Improving human cognition is an important goal with so many benefits," said Appelbaum, also a member of the Duke Institute for Brain Sciences. "Interestingly, our findings demonstrate one way in which visual experience has the capacity to improve cognition."
Source: Science Daily
A protein essential for metabolism and recently associated with neurodegenerative diseases also occurs in several brain-specific forms. This discovery emerged in the course of a research project funded by the Austrian Science Fund FWF, the findings of which have now been published in the journal Human Molecular Genetics. The scientists working on the project discovered a large new region in the genetic code of the protein PGC-1alpha. Previously unknown variations of the protein, which can be found specifically in the brain, are produced from this region. This discovery may provide tissue-specific starting points for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s.
PGC-1alpha is a real jack-of-all-trades. As a central regulator of metabolic genes that coordinate energy metabolism, the protein, which functions as a “transcriptional coactivator”, influences major body functions. The extent to which the protein also influences medical conditions like obesity, diabetes and metabolic syndrome is unclear, and was under further investigation as part of a research project funded by the Austrian Science Fund FWF. In the course of their research, however, the scientists stumbled on unexpected findings with a particular relevance for neurodegenerative diseases.
Major Difference
A research team headed by Prof. Wolfgang Patsch from the Departments of Pharmacology and Toxicology, and Laboratory Medicine at the Paracelsus Medical University established that the gene which codes for PGC-1alpha (PPARGC1A) is six times larger than hitherto assumed. A new promoter was actually found at some distance (ca. 580 kb) from the previously known gene. A promoter is a DNA segment usually occurring upstream from a gene that can ultimately control how that gene is expressed as a protein. The transmission of genetic information from DNA to RNA molecules, i.e. transcription, is an important intermediate step in this process.
Transcripts, which are produced from the newly discovered promoter, were now examined in detail as part of the research project. “These transcripts differ in important regions from those encoded by the previously characterized - reference - PPARGC1A locus. Based on these differences, we were able to show that these previously unknown transcripts are produced specifically in human brain cells and are at least as common there as the reference transcripts,” explains Dr. Selma M. Soyal, first author of the article currently published in Human Molecular Genetics. Further analyzes showed that the differences in the transcripts lead to the formation of proteins which differ from the protein that acts as a reference, in particular at the N-terminus. Other differences were found within the PGC-1alpha amino acid chain.
When the different PGC-1alpha proteins were localized in human cells (SH-SY5Y), another surprise awaited the scientists: whereas the reference protein was located mainly in the cell nucleus, one of the newly discovered variants was mainly found in the surrounding cytoplasm; another was found both in the nucleus and in the cytoplasm. According to Prof. Patsch: “It is likely that the differences we found in the transcripts influence mechanisms in the finished proteins which control their localization in the cell.”
A Protein With Impact
The detailed functional characterization of the brain-specific proteins could prove significant, as PGC-1alpha is associated with various neurodegenerative diseases such as Huntington’s disease, Parkinson’s and Alzheimer’s - a link that was also confirmed by the project. Using complex statistical analyses, sequence differences in the new promoter were examined in 1.706 Huntington patients as part of a collaboration with the European Huntington’s Disease Network. A clear correlation emerged here between different sequence patterns and the age of onset of the disease in the patients. In addition, the scientists were also able to show that the newly discovered promoter is active in nerve tissue. This indicates that it may actually play an important role in the only partly known links between PGC-1alpha and the neurodegenerative diseases in question.
Overall, the findings of this project, which is funded by the Austrian Science Fund FWF, indicate complex functions of PGC-1alpha in humans. If the scientists succeed in reaching a better understanding of this complexity, PGC-1alpha could provide new possibilities for future therapeutic intervention in key neurodegenerative diseases.
Snacking and BMI Linked to Double Effect of Brain Activity and Self-Control
ScienceDaily (July 23, 2012) — Snack consumption and BMI are linked to both brain activity and self-control, new research has found.
Snack consumption and BMI are linked to both brain activity and self-control, new research has found. (Credit: © farbkombinat / Fotolia)
The research, carried out by academics from the Universities of Exeter, Cardiff, Bristol, and Bangor, discovered that an individual’s brain ‘reward centre’ response to pictures of food predicted how much they subsequently ate. This had a greater effect on the amount they ate than their conscious feelings of hunger or how much they wanted the food,
A strong brain response was also associated with increased weight (BMI), but only in individuals reporting low levels of self-control on a questionnaire. For those reporting high levels of self-control a stronger brain response to food was actually related to a lower BMI.
This study, which is now published in the journal NeuroImage, adds to mounting evidence that overeating and increased weight are linked, in part, to a region of the brain associated with motivation and reward, called the nucleus accumbens. Responses in this brain region have been shown to predict weight gain in healthy weight and obese individuals, but only now have academics discovered that this is independent of conscious feelings of hunger, and that self-control also plays a key role.
Following these results, academics at the University of Exeter and Cardiff have begun testing ‘brain training’ techniques designed to reduce the influence of food cues on individuals who report low levels of self-control. Similar tests are being used to assist those with gambling or alcohol addiction.
Dr Natalia Lawrence of Psychology at the University of Exeter, lead researcher in both the original research and the new studies, said: “Our research suggests why some individuals are more likely to overeat and put on weight than others when confronted with frequent images of snacks and treats. Food images, such as those used in advertising, cause direct increases in activity in brain ‘reward areas’ in some individuals but not in others. If those sensitive individuals also struggle with self-control, which may be partly innate, they are more likely to be overweight. We are now developing computer programs that we hope will counteract the effects of this high sensitivity to food cues by training the brain to respond less positively to these cues.”
Twenty-five young, healthy females with BMIs ranging from 17-30 were involved in the study. Female participants were chosen because research shows females typically exhibit stronger responses to food-related cues. The hormonal changes during the menstrual cycle affect this reaction, so all participants were taking the monophasic combined oral contraceptive pill. Participants had not eaten for at least six hours to ensure they were hungry at the time of the scan and were given a bowl containing 150 g (four and a half packets) of potato chips to eat at the end of the study; they were informed that potato chip intake had been measured afterwards.
Researchers used MRI scanning to detect the participants’ brain activity while they were shown images of household objects, and food that varied in desirability and calorific content. After scanning, participants rated the food images for desirability and rated their levels of hunger and food craving. Results showed that participants’ brain responses to food (relative to objects) in the nucleus accumbens predicted how many potato chips they ate after the scan. However, participants’ own ratings of hunger and how much they liked and wanted the foods, including potato chips, were unrelated to their potato chip intake.
This study was funded by the Wales Institute of Cognitive Neuroscience.
What this study shows:
- Brain responses to food images vary considerably between individuals.
- Brain responses to food images but not conscious feelings of hunger or desire to eat predict subsequent potato chip consumption.
- Individuals’ reported levels of self-control influence whether this brain response is associated with a higher or lower BMI.
What this study does NOT show:
- Brain responses to food cues cause overeating.
- The associations reported here are true in everyone — only healthy young women were included.
- Whether our brain response and levels of self-control are learned or innate.
Source: Science Daily