Posts tagged science
Articles and news from the latest research reports.
A brain chemical that desynchronizes the cells in the biological clock helps the clock adjust more quickly to abrupt shifts in daily light/dark schedules such as those that plague modern life.
A small molecule called VIP, known to synchronize time-keeping neurons in the brain’s biological clock, has the startling effect of desynchronizing them at higher dosages, said a research team at Washington University in St. Louis.
Far from being catastrophic, the temporary loss of synchronization actually might be useful.
Neurons knocked for a loop by a burst of VIP are better able to re-synchronize to abrupt shifts in the light-dark cycle such as those that make jet lag or shift work so miserable. It takes tumbling cells only half as long as undisturbed cells to entrain to the new schedule, the scientists say in the Oct. 28 online early edition of the Proceedings of the National Academy of Sciences.
Resynching by jarring is familiar to everyone who has whacked a flickering analog TV to get it to sync or hit the ceiling near a fluorescent light in the hope that its ballast starts buzzing.
The scientists hope to find a way to coax the brain into releasing its own stores of VIP or to find other ways to deliberately cause tumbling so the body’s clock will reset to a new time. Such a treatment might help travelers, shift works and others who overtax the biological clock’s ability to entrain to environmental cues.
The finding is the latest to emerge from the lab of Erik Herzog, PhD, who has studied the body’s time-keeping mechanisms for 13 years at Washington University in St. Louis. His focus is on understanding the clock, but because most of us live against our biological clocks and research shows this leads to health problems ranging from obesity to depression, his work is likely to have practical payoffs.
Timing is everything
The master circadian clock in mammals is a knot of 20,000 nerve cells roughly the size of a quarter of a grain of rice called the suprachiasmatic nucleus (SCN). Each neuron in the SCN keeps time, but because they’re different cells, they have slightly different rhythms. Some run a bit fast and others a bit slow.
“They’re like a society where each cell has its own opinion on what time of day it is,” said Herzog, a profesor of biology in Arts & Sciences. “They need to agree on the time of day in order to coordinate daily rhythms in alertness and metabolism.”
The cells talk to one another through a molecule called VIP (vasoactive intestinal polypeptide), a small string of amino acids that they release and receive. It’s through VIP that cells tell one another what time they think it is, Herzog said. If you get rid of VIP or the receptor for VIP, the cells lose synchrony.
“We were trying to understand exactly when VIP is released and how it synchronized the cells,” Herzog said, “and Sungwon An, then a graduate student in my lab, discovered that when there was extra VIP around, the cells lost synchrony.
“That was really surprising for us,” he said. “We did a lot of experiments just to make sure the VIP we had bought wasn’t contaminated in some way.”
It turned out the effect was real. Above a critical level, the more VIP was released, the more desynchronized the cells became. “It’s almost as if at higher doses the cells become blind to the information from their neighbors,” Herzog said.
“Then we thought: ‘Well, if the cell rhythms are messed up and out of phase, the system may be more sensitive to environmental cues than it would be if all the cells were in sync.’” If it was more sensitive, it might be better able to adjust to the abrupt schedule shifts that characterize modern life.
They were encouraged in this line of thinking by a simulation of the SCN created by Linda Petzold, Kirsten Meeker, Rich Harang and Frank Doyle, all chemical engineers at the University of California, Santa Barbara. The numerical model predicted that increasing VIP would lead to phase tumbling (less synchrony) and accelerated entrainment.
Rapid entrainment to environmental cues is important, Herzog explained. The master clock has evolved to adjust to slow seasonal changes in light/dark schedules, but not to abrupt ones that are built into the fabric of modern life. Even the seemingly benign one-hour shift for daylight savings time increases the risk of fatal car crashes and of heart attacks.
“We were curious to see whether adding extra VIP would improve the ability of biological clocks to make big adjustments,” Herzog said. An, together with graduate student Cristina Mazuski and research scientist Daniel Granados-Fuentes, showed that a shot of VIP did in fact accelerate entrainment to a new light schedule.
“We found that in mice we could cut ‘jet lag’ in half by giving them a shot of VIP the day before we ‘flew them to a new time zone,’ by shifting their light schedule,” Herzog said.
“That’s really exciting, “ Herzog said. “This is the first demonstration that giving a bit more of a substance the brain already makes actually improves the way the circadian system functions. “
“We’re taking the system the brain uses to entrain to changes in the seasons and goosing it a bit so that it can adjust to bigger shifts in the light schedule,” he said.
“We’re hoping we’ll be able to find a way to coax the brain into releasing its own stores of VIP or a light trigger or other signal that mimics the effects of VIP,” Herzog said.
Snakes on the brain: Are primates hard-wired to see snakes?
Was the evolution of high-quality vision in our ancestors driven by the threat of snakes? Work by neuroscientists in Japan and Brazil is supporting the theory originally put forward by Lynne Isbell, professor of anthropology at the University of California, Davis.
In a paper published Oct. 28 in the journal Proceedings of the National Academy of Sciences, Isbell; Hisao Nishijo and Quan Van Le at Toyama University, Japan; and Rafael Maior and Carlos Tomaz at the University of Brasilia, Brazil; and colleagues show that there are specific nerve cells in the brains of rhesus macaque monkeys that respond to images of snakes.
The snake-sensitive neurons were more numerous, and responded more strongly and rapidly, than other nerve cells that fired in response to images of macaque faces or hands, or to geometric shapes. Isbell said she was surprised that more neurons responded to snakes than to faces, given that primates are highly social animals.
"We’re finding results consistent with the idea that snakes have exerted strong selective pressure on primates," Isbell said.
Isbell originally published her hypothesis in 2006, following up with a book, “The Fruit, the Tree and the Serpent” (Harvard University Press, 2009) in which she argued that our primate ancestors evolved good, close-range vision primarily to spot and avoid dangerous snakes.
Modern mammals and snakes big enough to eat them evolved at about the same time, 100 million years ago. Venomous snakes are thought to have appeared about 60 million years ago — “ambush predators” that have shared the trees and grasslands with primates.
Nishijo’s laboratory studies the neural mechanisms responsible for emotion and fear in rhesus macaque monkeys, especially instinctive responses that occur without learning or memory. Previous researchers have used snakes to provoke fear in monkeys, he noted. When Nishijo heard of Isbell’s theory, he thought it might explain why monkeys are so afraid of snakes.
"The results show that the brain has special neural circuits to detect snakes, and this suggests that the neural circuits to detect snakes have been genetically encoded," Nishijo said.
The monkeys tested in the experiment were reared in a walled colony and neither had previously encountered a real snake.
"I don’t see another way to explain the sensitivity of these neurons to snakes except through an evolutionary path," Isbell said.
Isbell said she’s pleased to be able to collaborate with neuroscientists.
"I don’t do neuroscience and they don’t do evolution, but we can put our brains together and I think it brings a wider perspective to neuroscience and new insights for evolution," she said.
(Source: news.ucdavis.edu)
Poor motor performance linked to poor academic skills in the first school years
Children with poor motor performance at the school entry were found to have poorer reading and arithmetic skills than their better performing peers during the first three years of school. However, no relationship was found between cardiovascular fitness and academic skills, according to a new study published in Medicine & Science in Sports & Exercise.
The study investigated the relationships of cardiovascular fitness and motor performance in the first grade to reading and arithmetic skills in grades 1–3 among 174 Finnish children as part of The Physical Activity and Nutrition (PANIC) Study at the University of Eastern Finland and The First Steps Study at the University of Jyväskylä. Children who performed poorly in agility, speed and manual dexterity tests and had poor overall motor performance in the first grade had lower reading and arithmetic test scores in grades 1–3 than children with better performance in motor tests. Especially children in the lowest motor performance third had poorer reading and arithmetic test scores than children in the other thirds. These associations were stronger in boys than girls. Unexpectedly, however, cardiovascular fitness was not related to academic skills.
The findings of the study highlight the importance of motor performance and movement skills over cardiovascular fitness for children’s school success during the first years of school. The academic development of children with poor motor performance should be carefully monitored and appropriate actions to support the development of reading, arithmetic and movement skills should be started when needed.
Nurturing may protect kids from brain changes linked to poverty
Growing up in poverty can have long-lasting, negative consequences for a child. But for poor children raised by parents who lack nurturing skills, the effects may be particularly worrisome, according to a new study at Washington University School of Medicine in St. Louis.
Among children living in poverty, the researchers identified changes in the brain that can lead to lifelong problems like depression, learning difficulties and limitations in the ability to cope with stress. The study showed that the extent of those changes was influenced strongly by whether parents were nurturing.
The good news, according to the researchers, is that a nurturing home life may offset some of the negative changes in brain anatomy among poor children. And the findings suggest that teaching nurturing skills to parents — particularly those living in poverty — may provide a lifetime benefit for their children.
The study is published online Oct. 28 and will appear in the November issue of JAMA Pediatrics.
Using magnetic resonance imaging (MRI), the researchers found that poor children with parents who were not very nurturing were likely to have less gray and white matter in the brain. Gray matter is closely linked to intelligence, while white matter often is linked to the brain’s ability to transmit signals between various cells and structures.
The MRI scans also revealed that two key brain structures were smaller in children who were living in poverty: the amygdala, a key structure in emotional health, and the hippocampus, an area of the brain that is critical to learning and memory.
“We’ve known for many years from behavioral studies that exposure to poverty is one of the most powerful predictors of poor developmental outcomes for children,” said principal investigator Joan L. Luby, MD, a Washington University child psychiatrist at St. Louis Children’s Hospital. “A growing number of neuroscience and brain-imaging studies recently have shown that poverty also has a negative effect on brain development.
“What’s new is that our research shows the effects of poverty on the developing brain, particularly in the hippocampus, are strongly influenced by parenting and life stresses that the children experience.”
Luby, a professor of psychiatry and director of the university’s Early Emotional Development Program, is in the midst of a long-term study of childhood depression. As part of the Preschool Depression Study, she has been following 305 healthy and depressed kids since they were in preschool. As the children have grown, they also have received MRI scans that track brain development.
“We actually stumbled upon this finding,” she said. “Initially, we thought we would have to control for the effects of poverty, but as we attempted to control for it, we realized that poverty was really driving some of the outcomes of interest, and that caused us to change our focus to poverty, which was not the initial aim of this study.”
In the new study, Luby’s team looked at scans from 145 children enrolled in the depression study. Some were depressed, others healthy, and others had been diagnosed with different psychiatric disorders such as ADHD (attention-deficit hyperactivity disorder). As she studied these children, Luby said it became clear that poverty and stressful life events, which often go hand in hand, were affecting brain development.
The researchers measured poverty using what’s called an income-to-needs ratio, which takes a family’s size and annual income into account. The current federal poverty level is $23,550 for a family of four.
Although the investigators found that poverty had a powerful impact on gray matter, white matter, hippocampal and amygdala volumes, they found that the main driver of changes among poor children in the volume of the hippocampus was not lack of money but the extent to which poor parents nurture their children. The hippocampus is a key brain region of interest in studying the risk for impairments.
Luby’s team rated nurturing using observations made by the researchers — who were unaware of characteristics such as income level or whether a child had a psychiatric diagnosis — when the children came to the clinic for an appointment. And on one of the clinic visits, the researchers rated parental nurturing using a test of the child’s impatience and of a parent’s patience with that child.
While waiting to see a health professional, a child was given a gift-wrapped package, and that child’s parent or caregiver was given paperwork to fill out. The child, meanwhile, was told that s/he could not open the package until the caregiver completed the paperwork, a task that researchers estimated would take about 10 minutes.
Luby’s team found that parents living in poverty appeared more stressed and less able to nurture their children during that exercise. In cases where poor parents were rated as good nurturers, the children were less likely to exhibit the same anatomical changes in the brain as poor children with less nurturing parents.
“Parents can be less emotionally responsive for a whole host of reasons,” Luby said. “They may work two jobs or regularly find themselves trying to scrounge together money for food. Perhaps they live in an unsafe environment. They may be facing many stresses, and some don’t have the capacity to invest in supportive parenting as much as parents who don’t have to live in the midst of those adverse circumstances.”
The researchers also found that poorer children were more likely to experience stressful life events, which can influence brain development. Anything from moving to a new house to changing schools to having parents who fight regularly to the death of a loved one is considered a stressful life event.
Luby believes this study could provide policymakers with at least a partial answer to the question of what it is about poverty that can be so detrimental to a child’s long-term developmental outcome. Because it appears that a nurturing parent or caregiver may prevent some of the changes in brain anatomy that this study identified, Luby said it is vital that society invest in public health prevention programs that target parental nurturing skills. She suggested that a key next step would be to determine if there are sensitive developmental periods when interventions with parents might have the most powerful impact.
“Children who experience positive caregiver support don’t necessarily experience the developmental, cognitive and emotional problems that can affect children who don’t receive as much nurturing, and that is tremendously important,” Luby said. “This study gives us a feasible, tangible target with the suggestion that early interventions that focus on parenting may provide a tremendous payoff.”
Rare Childhood Disease May Hold Clues to Treating Alzheimer’s and Parkinson’s
Scientists at Rutgers University studying the cause of a rare childhood disease that leaves children unable to walk by adolescence say new findings may provide clues to understanding more common neurodegenerative diseases like Alzheimer’s and Parkinson’s and developing better tools to treat them.
Courtesy of A-T Children’s Project: Andrew, 14, who has A-T disease with his brother, Brendan, 12, who did not inherit the rare childhood neurodegenerative disorder.
In today’s online edition of Nature Neuroscience, professors Karl Herrup, Ronald Hart and Jiali Li in the Department of Cell Biology and Neuroscience, and Alexander Kusnecov, associate professor in behavioral and systems neuroscience in the Department of Psychology, provide new information about A-T disease, a rare genetic childhood disorder that occurs in an estimated 1 in 40,000 births.
Children born with A-T disease have mutations in both of their copies of the ATM gene and cannot make normal ATM protein. This leads to problems in movement, coordination, equilibrium and muscle control as well as a number of other deficiencies outside the nervous system.
Using mouse and human brain tissue studies, Rutgers researchers found that without ATM, the levels of a regulatory protein known as EZH2 go up. Looking through the characteristics of A-T disease in cells in tissue culture and in brain samples from both humans and mice with ATM mutation, they found that the increase in EZH2 was a major contributing factor to the neuromuscular problems caused by A-T.
“We hope that this work will lead to new therapies to prevent symptoms in those with A-T disease,” says Hart. “But on a larger level, this research provides a strong clue toward understanding more common neurodegenerative disorders that may use similar pathways. “It is a theme that has not yet been examined.”
While the EZH2 protein has been shown to help determine whether genes get turned on or off, altering the body’s ability to perform biological functions, necessary for maintaining good health, the Rutgers study is the first time this protein – which can cause adverse health effects if there is too much of it – has been looked at in the mature nerve cells of the brain.
By reducing the excess EZH2 protein that accumulated in mice genetically engineered with A-T disease, and creating a better protein balance within the nerve cells, Rutgers scientists found that mice exhibited improved muscle control, movement and coordination.
In the study, mutant mice that had A-T disease and increased levels of EZH2 were “cured” when this excess EZH2 protein was reduced. The treated mice were able to stay on a rotating rod without falling off almost as long as the mice that did not have A-T disease. By contrast, untreated A-T animals lost their balance and fell off the device almost immediately. The mice were also studied in an open area setting. While the treated A-T mice and normal mice explored a wide area of the open field, the A-T mice, with their excess EZH2 protein, were not as adventurous and stayed behind.
Rutgers scientists say the implications of these findings now need to be validated in a clinical setting. They have begun working with the A-T Clinical Center at Johns Hopkins University, collecting blood samples from children with the disease as well as their parents who carry the genes in order to reprogram them into stem cells. This will allow scientists to create human neurons like those in A-T patients and study the mechanisms that lead from ATM mutations to nerve cell disease in more detail.
The hope is that this new information can be used to develop therapeutic drugs that may result in better neuromuscular control and coordination for those with A-T disease. In addition, the scientists will work to determine whether the EZH2 protein plays a role in other more common neurodegenerative diseases, like Parkinson’s and Alzheimer’s and could offer a target for developing drugs to treat those brain disorders.
“What is interesting about human health and this research in particular is that it illustrates how a disease that is thought of as 100 percent genetic, actually has a component that is sensitive to the environment,” says Herrup, lead author of the study.
(Source: news.rutgers.edu)
NIH-supported study identifies 11 new Alzheimer’s disease risk genes
An international group of researchers has identified 11 new genes that offer important new insights into the disease pathways involved in Alzheimer’s disease. The highly collaborative effort involved scanning the DNA of over 74,000 volunteers—the largest genetic analysis yet conducted in Alzheimer’s research—to discover new genetic risk factors linked to late-onset Alzheimer’s disease, the most common form of the disorder.
By confirming or suggesting new processes that may influence Alzheimer’s disease development—such as inflammation and synaptic function—the findings point to possible targets for the development of drugs aimed directly at prevention or delaying disease progression.
Supported in part by the National Institute on Aging (NIA) and other components of the National Institutes of Health, the International Genomic Alzheimer’s Project (IGAP) reported its findings online in Nature Genetics on Oct. 27, 2013. IGAP is comprised of four consortia in the United States and Europe which have been working together since 2011 on genome-wide association studies (GWAS) involving thousands of DNA samples and shared datasets. GWAS are aimed at detecting the subtle gene variants involved in Alzheimer’s and defining how the molecular mechanisms influence disease onset and progression.
"Collaboration among researchers is key to discerning the genetic factors contributing to the risk of developing Alzheimer’s disease," said Richard J. Hodes, M.D., director of the NIA. "We are tremendously encouraged by the speed and scientific rigor with which IGAP and other genetic consortia are advancing our understanding."
The search for late-onset Alzheimer’s risk factor genes had taken considerable time, until the development of GWAS and other techniques. Until 2009, only one gene variant, Apolipoprotein E-e4 (APOE-e4), had been identified as a known risk factor. Since then, prior to today’s discovery, the list of known gene risk factors had grown to include other players—PICALM, CLU, CR1, BIN1, MS4A, CD2AP, EPHA1, ABCA7, SORL1 and TREM2.
IGAP’s discovery reported today of 11 new genes strengthens evidence about the involvement of certain pathways in the disease, such as the role of the SORL1 gene in the abnormal accumulation of amyloid protein in the brain, , a hallmark of Alzheimer’s disease. It also offers new gene risk factors that may influence several cell functions, to include the ability of microglial cells to respond to inflammation.
The researchers identified the new genes by analyzing previously studied and newly collected DNA data from 74,076 older volunteers with Alzheimer’s and those free of the disorder from 15 countries. The new genes (HLA-DRB5/HLA0DRB1, PTK2B, SLC24A4-0RING3, DSG2, INPP5D, MEF2C, NME8, ZCWPW1, CELF1, FERMT2 and CASS4) add to a growing list of gene variants associated with onset and progression of late-onset Alzheimer’s. Researchers will continue to explore the roles played by these genes, to include:
- How SORL1 and CASS4 influence amyloid, and how CASS4 and FERMT2 affect tau, another protein hallmark of Alzheimer’s disease
- How inflammation is influenced by HLA-DRB5/DRB1, INPP5D, MEF2C, CR1 and TREM2
- How SORL1affects lipid transport and endocytosis (or protein sorting within cells)
- How MEF2C and PTK2B influence synaptic function in the hippocampus, a brain region important to learning and memory
- How CASS4, CELF1, NME8 and INPP5 affect brain cell function
The study also brought to light another 13 variants that merit further analysis.
"Interestingly, we found that several of these newly identified genes are implicated in a number of pathways," said Gerard Schellenberg, Ph.D., University of Pennsylvania School of Medicine, Philadelphia, who directs one of the major IGAP consortia. "Alzheimer’s is a complex disorder, and more study is needed to determine the relative role each of these genetic factors may play. I look forward to our continued collaboration to find out more about these—and perhaps other—genes."
(Image: National Institute on Aging)
Neuroscientists discover new ‘mini-neural computer’ in the brain
Dendrites, the branch-like projections of neurons, were once thought to be passive wiring in the brain. But now researchers at the University of North Carolina at Chapel Hill have shown that these dendrites do more than relay information from one neuron to the next. They actively process information, multiplying the brain’s computing power.
“Suddenly, it’s as if the processing power of the brain is much greater than we had originally thought,” said Spencer Smith, PhD, an assistant professor in the UNC School of Medicine.
His team’s findings, published October 27 in the journal Nature, could change the way scientists think about long-standing scientific models of how neural circuitry functions in the brain, while also helping researchers better understand neurological disorders.
Axons are where neurons conventionally generate electrical spikes, but many of the same molecules that support axonal spikes are also present in the dendrites. Previous research using dissected brain tissue had demonstrated that dendrites can use those molecules to generate electrical spikes themselves, but it was unclear whether normal brain activity uses those dendritic spikes. For example, could dendritic spikes be involved in how we see?
The answer, Smith’s team found, is yes. Dendrites effectively act as mini-neural computers, actively processing neuronal input signals themselves.
Directly demonstrating this required a series of intricate experiments that took years and spanned two continents, beginning in senior author Michael Hausser’s lab at University College London, and being completed after Smith and Ikuko Smith, PhD, DVM, set up their own lab at the University of North Carolina. They used patch-clamp electrophysiology to attach a microscopic glass pipette electrode, filled with a physiological solution, to a neuronal dendrite in the brain of a mouse. The idea was to directly “listen” in on the electrical signaling process.
“Attaching the pipette to a dendrite is tremendously technically challenging,” Smith said. “You can’t approach the dendrite from any direction. And you can’t see the dendrite. So you have to do this blind. It’s like fishing but all you can see is the electrical trace of a fish.” And you can’t use bait. “You just go for it and see if you can hit a dendrite,” he said. “Most of the time you can’t.”
But Smith built his own two-photon microscope system to make things easier.
Once the pipette was attached to a dendrite, Smith’s team took electrical recordings from individual dendrites within the brains of anesthetized and awake mice. As the mice viewed visual stimuli on a computer screen, the researchers saw an unusual pattern of electrical signals – bursts of spikes – in the dendrite.
Smith’s team then found that the dendritic spikes occurred selectively, depending on the visual stimulus, indicating that the dendrites processed information about what the animal was seeing.
To provide visual evidence of their finding, Smith’s team filled neurons with calcium dye, which provided an optical readout of spiking. This revealed that dendrites fired spikes while other parts of the neuron did not, meaning that the spikes were the result of local processing within the dendrites.
Study co-author Tiago Branco, PhD, created a biophysical, mathematical model of neurons and found that known mechanisms could support the dendritic spiking recorded electrically, further validating the interpretation of the data.
“All the data pointed to the same conclusion,” Smith said. “The dendrites are not passive integrators of sensory-driven input; they seem to be a computational unit as well.”
His team plans to explore what this newly discovered dendritic role may play in brain circuitry and particularly in conditions like Timothy syndrome, in which the integration of dendritic signals may go awry.
Epigenetics: A Key to Controlling Acute and Chronic Pain
Epigenetics, the study of changes in gene expression through mechanisms outside of the DNA structure, has been found to control a key pain receptor related to surgical incision pain, according to a study in the November issue of Anesthesiology. This study reveals new information about pain regulation in the spinal cord.
“Postoperative pain is an incompletely understood and only partially controllable condition that can result in suffering, medical complications, unplanned hospital admissions and disappointing surgery outcomes,” said David J. Clark, M.D., Ph.D., Professor of Anesthesia at Stanford University and Director of Pain Management at the VA Palo Alto Health Care System. “We know that histone acetylation and deacetylation modifies many cellular processes and produces distinct outcomes. In this study we found that histones can epigenetically activate or silence gene expression to either increase or decrease incision pain.”
Human DNA is wrapped around proteins called histones, much like thread is wrapped around a spool. When a histone undergoes deacetylation, the DNA wraps more tightly around the spool, effectively silencing genes. Conversely, when it undergoes acetylation, the DNA is loosened, allowing for transcription or modifications of genes to occur.
In this study, groups of mice had small surgical incisions made in their hind paws after being anesthetized. These mice were then regularly injected with suberoylanilide hydroxamic acid (SAHA), which prevents deacetylation (thus promoting gene transcription), or anacardic acid, which prevents acetylation (thus reducing gene transcription). The authors tested the animals daily for the degree of pain sensitivity in their hind paws.
The study found that regulation of histone acetylation can control pain sensitization after an incision. Specifically, maintaining histone in a relatively deacetylated state reduced hypersensitivity after incision. This is due, in part, to the epigenetic regulation of a specific gene known as CXCR2 and one of its chemokine ligands (KC). The authors also found that these epigenetic changes far outlasted the recovery of animals from their incisions, a property that might help explain why some patients suffer from chronic postoperative pain. Study authors suggest that looking into the roles of these epigenetic mechanisms may help scientists find new ways to treat or prevent acute and chronic postoperative pain in the future.
“Epigenetics is a relatively underappreciated area of science, but the discoveries yet to be made in this field will be many,” said Dr. Clark. “While fascinating information has been found by studying specific genes, we need to bridge the gap in science and focus on groups or systems of many genes simultaneously, which could be give us clues to greater breakthroughs in pain control and other areas of medicine.”
(Source: newswise.com)
Ultrasound device combined with clot-buster safe for stroke
A study led by researchers at The University of Texas Health Science Center at Houston (UTHealth) showed that a hands-free ultrasound device combined with a clot-busting drug was safe for ischemic stroke patients.
The results of the phase II pilot study were reported today in the American Heart Association journal Stroke. Lead author is Andrew D. Barreto, M.D., assistant professor of neurology in the Stroke Program at the UTHealth Medical School. Principal investigator is James C. Grotta, M.D., professor and chair of the Department of Neurology at the UTHealth Medical School, the Roy M. & Phyllis Gough Huffington Distinguished Chair and co-director of the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center.
The device, which uses UTHealth technology licensed to Cerevast Therapeutics, Inc., is placed on the stroke patient’s head and delivers ultrasound to enhance the effectiveness of the clot-busting drug tissue plasminogen activator (tPA). Unlike the traditional hand-held ultrasound probe that’s aimed at a blood clot, the hands-free device used 18 separate probes and showers the deep areas of the brain where large blood clots cause severe strokes.
“Our goal is to open up more arteries in the brain and help stroke patients recover,” said Barreto, an attending physician at Mischer Neuroscience Institute. “This technology would have a significant impact on patients, families and society if we could improve outcomes by another 10 percent or more by adding ultrasound to patients who’ve already received tPA.”
In the first study of its kind, 20 moderately severe ischemic stroke patients (12 men and eight women, average age 63 years) received intravenous tPA up to 4.5 hours after symptoms occurred and two hours exposure to 2-MHz pulsed wave transcranial ultrasound.
Researchers reported that 13 (or 65 percent) patients either returned home or to rehabilitation 90 days after the combination treatment. After three months, five of the 20 patients had no disability from the stroke and one had slight disability.
(Source: uthouston.edu)
New study shows promise for first effective medicine to treat cocaine dependence
New research published in JAMA Psychiatry reveals that topiramate, a drug approved by the U.S. Food and Drug Administration (FDA) to treat epilepsy and migraine headaches, also could be the first reliable medication to help treat cocaine dependence.
The study, led by Bankole A. Johnson, DSc. MD., MB.ChB., MPhil., chairman of the Department of Psychiatry at the University of Maryland School of Medicine and head of the School’s new Brain Science Research Consortium Unit, with support from the National Institutes of Health and Agency for Healthcare Research and Quality, is one of the first to establish a pharmacological treatment for cocaine addiction, for which there are currently no FDA-approved medications.
Addiction affects 13.2 to 19.7 million cocaine users worldwide. Cocaine is responsible for more U.S. emergency room visits than any other illegal drug. Cocaine harms the brain, heart, blood vessels, and lungs — and can even cause sudden death.
Professor Johnson, one of the nation’s leading neuroscientists and psychopharmacologists, had previously found that topiramate was a safe and effective treatment for alcohol dependence compared with placebo.
In releasing the new study, Professor Johnson, who conducted the research when he was with Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia, provided full disclosures, which follow the text of this news announcement.*
The study enrolled 142 participants, aged 18 years or older, seeking treatment for cocaine dependence. Following enrollment, participants were randomly assigned into a topiramate group or placebo group. Neither the participants nor the healthcare professionals administering the treatment knew who was in which group (double-blinded study).
Using an intent-to-treat analysis, the researchers found that topiramate was more efficacious than placebo at increasing the participants’ weekly proportion of cocaine nonuse days and in increasing the likelihood that participants would have cocaine-free weeks. Furthermore, compared with placebo, topiramate also was significantly associated with a decrease in craving for cocaine and an improvement in participants’ global functioning.
The study investigators also observed few side effects due to drug treatment. In general, participants in the topiramate group experienced mild side-effects, including abnormal tingling skin sensations, taste distortions, anorexia, and difficulty concentrating.
"Our findings reveal that topiramate is a safe and robustly efficacious medicine for the treatment of cocaine dependence, and has the potential to make a major contribution to the global health crisis of addiction," Professor Johnson said. "However, topiramate treatment also is associated with glaucoma, and higher doses of the drug can increase the risk of side effects; therefore, caution must be exercised when prescribing the drug, especially when given in high doses."
These results build upon earlier work from Professor. Johnson’s group which indicated that individuals dependent on cocaine, but not seeking treatment, who took topiramate were more likely to experience reduced cravings and preference for cocaine, compared with placebo. The findings of the current study indicate that topiramate may be even more effective in treating people with addiction who actively want to quit using cocaine.
"Because topiramate is the first medication to demonstrate a robust therapeutic effect for the treatment of cocaine or alcohol dependence, its fundamental neurochemical effects provide important clues as to common links in the neurobiological basis of the addictive process in general," remarked Professor Johnson. "These findings also add to our understanding of how addiction affects the brain because it demonstrates the unique concept that dual neurotransmitter modulation, by simultaneously augmenting the inhibitory action of gamma amino butyric acid and inhibiting the excitatory effects of glutamate, can result in therapeutic effects that reduce the propensity to use cocaine."
*Editor’s Notes:
A. Statement of Disclosure
Professor Johnson reported serving as a consultant for Johnson & Johnson (Ortho-McNeil Janssen Scientific Affairs, LLC) the manufacturer of topiramate, from 2003-2008 and currently has no affiliation with that Company, Transcept Pharmaceuticals, Inc. from 2006-2008, Eli Lilly and Company from 2009-2010, and Organon from 2007-2010. He currently consults for D&A Pharma, ADial Pharmaceuticals, LLC, (with which he also serves as chairman), and Psychological Education Publishing Company (PEPCo), LLC. Topiramate is currently available as a generic medicine in the USA, and Professor Johnson has no commercial affiliation with any generic manufacturer of topiramate. Dr. Liu reported serving as a consultant for Celladon Corporation. No other disclosures were reported.
B. Funding/ Support
This study was supported by NIH grants 501 DAO17296-04 and 5 RC1AA019274-02, and Agency for Healthcare Research and Quality grant 7 RO1 HS020263092.