Posts tagged science
Articles and news from the latest research reports.
Combination of Two Imaging Techniques Allows New Insights into Brain Function
The ability to measure brain functions non-invasively is important both
for clinical diagnoses and research in Neurology and Psychology. Two main imaging techniques are used: positron emission tomography (PET), which reveals metabolic processes in the brain; and activity of different brain regions is measured on the basis of the cells’ oxygen consumption by magnetic resonance imaging (MRI). A direct comparison of PET and MRI measurements was previously difficult because each had to be performed in a separate machine.
Researchers from the Werner Siemens Imaging Center at the University of Tübingen under the direction of Professor Bernd J. Pichler in collaboration with the Department of Diagnostic and Interventional Radiology, University Hospital Tübingen, and the Tübingen Max Planck Institute for Intelligent Systems have now successfully combined both methods. The researchers are able to explore functional processes in the brain in detail and can better assess what course of action to take. These results were achieved by the use of a PET insert enabling complementary, simultaneous PET/MRI scans. It was developed and built at the University of Tübingen.
The researchers could identify in certain regions a mismatch between glucose metabolism related brain activation measured with PET and oxygenation related signals, measured with MRI. Furthermore information about functional connectivity in the brain could be derived from MRI and from dynamic PET data. These results help to further decipher the nature of brain function, and are ultimately useful for basic research as well as clinical practice. The study, by lead author Dr. Hans Wehrl of Professor Bernd J. Pichler’s research team is soon to be published in the journal “Nature Medicine”.
In PET imaging the distribution of a weakly radioactive substance is shown in cross sections of the body, enabling doctors to see many different metabolic and physiological functions at work. Functional MRI (fMRI) allows researchers to depict changes in blood oxygenation that are associated with brain function. This measurement of functional active brain regions is also important for the planning of brain surgeries, where particular care must be taken in certain areas. The ability to collect different kinds of data from different scans simultaneously represents a major step forward in the fields using these technologies.
(Source: alphagalileo.org)
Researchers discover how inhibitory neurons behave during critical periods of learning
We’ve all heard the saying “you can’t teach an old dog new tricks.” Now neuroscientists are beginning to explain the science behind the adage.
For years, neuroscientists have struggled to understand how the microcircuitry of the brain makes learning easier for the young, and more difficult for the old. New findings published in the journal Nature by Carnegie Mellon University, the University of California, Los Angeles and the University of California, Irvine show how one component of the brain’s circuitry — inhibitory neurons — behave during critical periods of learning.
The brain is made up of two types of cells — inhibitory and excitatory neurons. Networks of these two kinds of neurons are responsible for processing sensory information like images, sounds and smells, and for cognitive functioning. About 80 percent of neurons are excitatory. Traditional scientific tools only allowed scientists to study the excitatory neurons.
"We knew from previous studies that excitatory cells propagate information. We also knew that inhibitory neurons played a critical role in setting up heightened plasticity in the young, but ideas about what exactly those cells were doing were controversial. Since we couldn’t study the cells, we could only hypothesize how they were behaving during critical learning periods," said Sandra J. Kuhlman, assistant professor of biological sciences at Carnegie Mellon and member of the joint Carnegie Mellon/University of Pittsburgh Center for the Neural Basis of Cognition.
The prevailing theory on inhibitory neurons was that, as they mature, they reach an increased level of activity that fosters optimal periods of learning. But as the brain ages into adulthood and the inhibitory neurons continue to mature, they become even stronger to the point where they impede learning.
Newly developed genetic and imaging technologies are now allowing researchers to visualize inhibitory neurons in the brain and record their activity in response to a variety of stimuli. As a postdoctoral student at UCLA in the laboratory of Associate Professor of Neurobiology Joshua T. Trachtenberg, Kuhlman and her colleagues used these new techniques to record the activity of inhibitory neurons during critical learning periods. They found that, during heightened periods of learning, the inhibitory neurons didn’t fire more as had been expected. They fired much less frequently — up to half as often.
"When you’re young you haven’t experienced much, so your brain needs to be a sponge that soaks up all types of information. It seems that the brain turns off the inhibitory cells in order to allow this to happen," Kuhlman said. "As adults we’ve already learned a great number of things, so our brains don’t necessarily need to soak up every piece of information. This doesn’t mean that adults can’t learn, it just means when they learn, their neurons need to behave differently."
Study in mice links cocaine use to new brain structures
Mice given cocaine showed rapid growth in new brain structures associated with learning and memory, according to a research team from the Ernest Gallo Clinic and Research Center at UC San Francisco. The findings suggest a way in which drug use may lead to drug-seeking behavior that fosters continued drug use, according to the scientists.
The researchers used a microscope that allowed them to peer directly into nerve cells within the brains of living mice, and within two hours of giving a drug they found significant increases in the density of dendritic spines – structures that bear synapses required for signaling – in the animals’ frontal cortex. In contrast, mice given saline solution showed no such increase.
The researchers also found a relationship between the growth of new dendritic spines and drug-associated learning. Specifically, mice that grew the most new spines were those that developed the strongest preference for being in the enclosure where they received cocaine rather than in the enclosure where they received saline. The team published its findings online in Nature Neuroscience on August 25, 2013.
"This gives us a possible mechanism for how drug use fuels further drug-seeking behavior," said principal investigator Linda Wilbrecht, PhD, a Gallo investigator now at UC Berkeley, but who led the research while she was on the UCSF faculty.
"It’s been observed that long-term drug users show decreased function in the frontal cortex in connection with mundane cues or tasks, and increased function in response to drug-related activity or information," Wilbrecht said. "This research suggests how the brains of drug users might shift toward those drug-related associations."
In all living brains there is a baseline level of creation of new spines in response to, or in anticipation of, day-to-day learning, Wilbrecht said. By enhancing this growth, cocaine might be a super-learning stimulus that reinforces learning about the cocaine experience, she said.
The frontal cortex, which Wilbrecht called the “steering wheel” of the brain, controls functions such as long-term planning, decision-making and other behaviors involving higher reasoning and discipline.
The brain cells in the frontal cortex that Wilbrecht and her team studied regulate the output of this brain region, and may play a key role in decision-making. “These neurons, which are directly affected by cocaine use, have the potential to bias decision-making,” she said.
Wilbrecht said the findings could potentially advance research in human addiction “by helping us identify what is going awry in the frontal cortexes of drug-addicted humans, and by explaining how drug-related cues come to dominate the brain’s decision-making processes.”
In the first of a series of experiments, the scientists gave cocaine injections to one group of mice and saline injections to another. The next day, they observed the animals’ brain cells using a 2-photon laser scanning microscope. They were surprised to discover that even after the first dose, the mice treated with cocaine grew more new dendritic spines than the saline-treated mice.
In another experiment, they observed the mice before cocaine or saline treatment and then two hours afterward, and discovered that the animals that received cocaine were developing new dendritic spines within two hours after receiving the drug. Furthermore, the next morning, cocaine-induced spines accounted for almost four times more connections among nerve cells than was observed in saline-treated animals.
In a third experiment, the researchers for a week gave the mice cocaine in one distinctive chamber and saline in another, using identical procedures. Each chamber had its own characteristic visual design, texture and smell to distinguish it from the other chamber. They then let the mice choose which chamber to go to.
"The animals that showed the highest quantity of robust dendritic spines – the spines with the greatest likelihood of developing into synapses – showed the greatest change in preference toward the chamber where they received the cocaine," said Wilbrecht. "This suggests that the new spines might be material for the association that these mice have learned to make between the chamber and the drug."
Wilbrecht noted that the research would not have been possible without live brain imaging via the 2-photon laser scanning microscope, which was developed in 2002. “I grew up at the time of the famous public service campaign that showed a pan of frying eggs with the message, ‘this is your brain on drugs,’” recalled Wilbrecht. “Now, with this microscope, we can actually say, ‘this is a brain cell on drugs.’”
(Source: eurekalert.org)
How the Brain Remembers Pleasure and Its Implications for Addiction
Key details of the way nerve cells in the brain remember pleasure are revealed in a study by University of Alabama at Birmingham (UAB) researchers published today in the journal Nature Neuroscience. The molecular events that form such “reward memories” appear to differ from those created by drug addiction, despite the popular theory that addiction hijacks normal reward pathways.
Brain circuits have evolved to encourage behaviors proven to help our species survive by attaching pleasure to them. Eating rich food tastes good because it delivers energy and sex is desirable because it creates offspring. The same systems also connect in our mind’s environmental cues with actual pleasures to form reward memories.
This study in rats supports the idea that the mammalian brain features several memory types, each using different circuits, with memories accessed and integrated as needed. Ancient memory types include those that remind us what to fear, what to seek out (reward), how to move (motor memory) and navigate (place memory). More recent developments enable us to remember the year Columbus sailed and our wedding day.
“We believe reward memory may serve as a good model for understanding the molecular mechanisms behind many types of learning and memory,” said David Sweatt, Ph.D., chair of the UAB Department of Neurobiology, director of the Evelyn F. McKnight Brain Institute at UAB and corresponding author for the study. “Our results provide a leap in the field’s understanding of reward-learning mechanisms and promise to guide future attempts to solve related problems such as addiction and criminal behavior.”
The study is the first to illustrate that reward memories are created by chemical changes that influence known memory-related genes in nerve cells within a brain region called the ventral tegmental area, or VTA. Experiments that blocked those chemical changes — a mix of DNA methylation and demethylation — in the VTA prevented rats from forming new reward memories.
Methylation is the attachment of a methyl group (one carbon and three hydrogens) to a DNA chain at certain spots (cytosine bases). When methylation occurs near a gene or inside a gene sequence, it generally is thought to turn the gene off and its removal is thought to turn the gene on. This back-and-forth change affects gene expression without changing the code we inherit from our parents. Operating outside the genetic machinery proper, epigenetic changes enable each cell type to do its unique job and to react to its environment.
Furthermore, a stem cell in the womb that becomes bone or liver cells must “remember” its specialized nature and pass that identity to its descendants as they divide and multiply to form organs. This process requires genetic memory, which largely is driven by methylation. Note, most nerve cells do not divide and multiply as do other cells. They can’t, according to one theory, because they put their epigenetic mechanisms to work making actual memories.
Natural pleasure versus addiction
The brain’s pleasure center is known to proceed through nerve cells that signal using the neurochemical dopamine and generally is located in the VTA. Dopaminergic neurons exhibit a “remarkable capacity” to pass on pleasure signals. Unfortunately, the evolutionary processes that attached pleasure to advantageous behaviors also accidentally reinforced bad ones.
Addiction to all four major classes of abused drugs — psychostimulants, opiates, ethanol and nicotine — has been linked to increased dopamine transmission in the same parts of the brain associated with normal reward processing. Cues that predict both normal reward and effects of cocaine or alcohol also make dopamine nerve cells fire as do the experiences they recall. That had led to idea that drug addiction must take over normal reward-memory nerve pathways.
Along those lines, past research has argued that dopamine-producing neurons in the VTA — and in a region that receives downstream dopamine signals from the VTA called the nucleus accumbens (NAC) — both were involved in natural reward and drug-addiction-based memory formation. While that may true to some extent, this study revealed that blocking methylation in the VTA with a drug stopped the ability of rats to attach rewarding experiences to remembered cues but doing so in the NAC did not.
“We observed an important distinction, not in circuitry, but instead in the epigenetic regulation of that circuitry between natural reward responses and those that occur downstream with drugs of abuse or psychiatric illness,” said Jeremy Day, Ph.D., a post-doctoral scholar in Sweatt’s lab and first author for this study. “Although drug experiences may co-opt normal reward mechanisms to some extent, our results suggest they also may engage entirely separate epigenetic mechanisms that contribute only to addiction and that may explain its strength.”
To investigate the molecular and epigenetic changes in the VTA, researchers took their cue from 19th century Russian physiologist Ivan Pavlov, who was the first to study the phenomenon of conditioning. By ringing a bell each day before giving his dogs food, Pavlov soon found that the dogs would salivate at the sound of the bell.
In this study, rats were trained to associate a sound tone with the availability of sugar pellets in their feed ports. This same animal model has been used to make most discoveries about how human dopamine neurons work since the 1990s, and most approved drugs that affect the dopamine system (e.g. L-Dopa for Parkinson’s) were tested in it before being cleared for human trials.
To separate the effects of memory-related brain changes from those arising from the pleasure of the eating itself, the rats were separated into three groups. Rats in the “CS+” rats got sugar pellets each time they heard a sound cue. The “CS–” group heard the sound the same number of times and received as many sugar pellets — but never together. A third tone-only group heard the sounds but never received sugar rewards.
Rats that always received sugar with the sound cue were found to poke their feed ports with their noses at least twice as often during this cue as control rats after three, 25-sound-cue sessions. Nose pokes are an established measure of the degree to which a rat has come to associate a cue with the memory of a tasty treat.
The team found that those CS+ rats (sugar paired with sound) that were better at forming reward memories had significantly higher expression of the genes Egr1 and Fos than control rats These genes are known to regulate memory in other brain regions by fine-tuning the signaling capacity of the connections between nerve cells. In a series of experiments, the team next revealed the methylation and demethylation pattern that drove the changes in gene expression seen as memories formed.
The study demonstrated that reward-related experiences caused both types of DNA methylation known to regulate gene expression.
One type involves attaching methyl groups to pieces of DNA called promoters, which reside immediately upstream of individual gene sequences (between genes), that tell the machinery that follows genetic instructions to “start reading here.” The attachment of a methyl group to a promoter generally interferes with this and silences a nearby gene. However, ancient organisms such as plants and insects have less methylation between their genes, and more of it within the coding regions of the genes themselves (within gene bodies). Such gene-body methylation has been shown to encourage rather than silence gene expression.
Specifically, the team reported that two sites in the promoter for Egr1 gene were demethylated during reward experiences and, to a greater degree, in rats that associated the sugar with the sound cue. Conversely, spots within the gene body of both Egr1 and Fos underwent methylation as reward memories formed.
“When designing therapeutic treatments for psychiatric illness, addictions or memory disorders, you must profoundly understand the function of the biological systems you’re working with,” Day said. “Our field has learned from experience that attempts to treat addiction with something that globally impairs normal reward perception or reward memories do not succeed. Our study suggests the possibility that future treatments could dial down drug addiction or mental illness without affecting normal rewards.”
(Image: Corbis)
Nicotine exposure gives baby rats addictive personalities
Results suggest explanation for why people exposed to nicotine in the womb are more likely to become smokers.
Exposure to nicotine in the womb increases the production of brain cells that stimulate appetite, leading to overconsumption of nicotine, alcohol and fatty foods in later life, according to a new study in rats.
Smoking during pregnancy is known to alter fetal brain development and increase the risk of premature birth, low birth weight and miscarriage. Prenatal exposure to nicotine also increases the likelihood of tobacco use and nicotine addiction in later life, but exactly how is unclear.
To understand the mechanisms behind this effect, Sarah Leibowitz, a behavioural neurobiologist at the Rockefeller University in New York, and her colleagues injected pregnant rats with small doses of nicotine — which the researchers say are comparable to the amount a pregnant woman would get from smoking one cigarette a day — and then examined the brains and behaviour of the offspring.
In a paper published in Journal of Neuroscience, they found that nicotine increased the production of specific types of neurons in the amygdala and hypothalamus. These cells produce orexin, enkephalin and melanin-concentrating hormone, neuropeptides that stimulate appetite and increase food intake.
Rats exposed to nicotine in the womb had more of these cells and produced more of the neuropeptides than those that were not, and this had long-term consequences on their behaviour. As adolescents, they not only self-administered more nicotine, but also ate more fat-rich food and drank more alcohol.
“These peptide systems stimulate food intake,” says Leibowitz, “but we found that they similarly increase the consumption of drugs and stimulate the brain’s reward mechanisms that promote addiction and substance abuse.”
Leibowitz notes that children whose mothers smoked during pregnancy are more likely to smoke themselves during adolescence and adulthood. Her team’s findings suggest a possible mechanism for that.
The use of nicotine patches or e-cigarettes during pregnancy could have a similar effect. “Whether given subcutaneously, as in our study, or via smoking or patches, the same amount of nicotine would still get into the brain to affect neuronal development and function,” Leibowitz says.
The results highlight the toxic effects of nicotine exposure on brain development, says George Koob, a neurobiologist at the Scripps Research Institute in La Jolla, California. He also adds that the study casts new light on the role of these neuropeptides in reward and motivation.
In earlier work, Leibowitz and her colleagues showed that rats exposed to fat and alcohol in the womb likewise overconsume these substances as adolescents. “Our studies make it very clear that neuronal development in utero is highly sensitive to these substances,” she says, “with each promoting their overconsumption and addictive-like behaviour in the offspring.”
She and her collaborators are now comparing the effects of nicotine, fat and alcohol to learn more about how this promotion occurs. They are also exploring ways to reverse the effects of prenatal exposure to these substances, thus preventing their overconsumption in later life, which could lead to addiction and obesity.
Russell Foster is a circadian neuroscientist: He studies the sleep cycles of the brain. And he asks: What do we know about sleep? Not a lot, it turns out, for something we do with one-third of our lives. In this talk, Foster shares three popular theories about why we sleep, busts some myths about how much sleep we need at different ages — and hints at some bold new uses of sleep as a predictor of mental health.
Russell Foster studies sleep and its role in our lives, examining how our perception of light influences our sleep-wake rhythms.
Brain Atrophy Seen in Patients With Diabetes
Brain atrophy rather than cerebrovascular lesions may explain the relationship between type 2 diabetes mellitus (T2DM) and cognitive impairment, according to a study published online Aug. 12 in Diabetes Care.
Chris Moran, M.B., B.Ch., from Monash University in Melbourne, Australia, and colleagues analyzed magnetic resonance imaging scans and cognitive tests in 350 participants with T2DM and 363 participants without T2DM. In a blinded fashion, cerebrovascular lesions (infarcts, microbleeds, and white matter hyperintensity [WMH] volume) and atrophy (gray matter, white matter, and hippocampal volumes) were evaluated.
The researchers found that T2DM was associated with significantly more cerebral infarcts and significantly lower total gray, white, and hippocampal volumes, but not with microbleeds or WMH. Gray matter loss was distributed mainly in medial temporal, anterior cingulate, and medial frontal lobe locations in patients with T2DM, while white matter loss was distributed in frontal and temporal regions. Independent of age, sex, education, and vascular risk factors, T2DM was associated with significantly poorer visuospatial construction, planning, visual memory, and speed. When adjusting for hippocampal and total gray volumes, the strength of these associations was cut by almost one-half, but was unchanged with adjustments for cerebrovascular lesions or white matter volume.
"Cortical atrophy in T2DM resembles patterns seen in preclinical Alzheimer’s disease," the authors write. "Neurodegeneration rather than cerebrovascular lesions may play a key role in T2DM-related cognitive impairment."
(Source: pri-med.com)
Depressed people have a more accurate perception of time
People with mild depression underestimate their talents. However, new research carried out researchers at the University of Limerick and the University of Hertfordshire shows that depressed people are more accurate when it comes to time estimation than their happier peers.
Depressed people often appear to distort the facts and view their lives more negatively than non-depressed people. Feelings of helplessness, hopelessness and worthlessness and of being out of control are some of the main symptoms of depression. For these people time seems to pass slowly and they will often use phrases such as “time seems to drag” to describe their experiences and their life. However, depressed people sometimes have a more accurate perception of reality than their happier friends and family who often look at life through rose-tinted glasses and hope for the best.
Dr Rachel Msetfi, senior lecturer in psychology, University of Limerick and one of the studies authors, said: “We found that depressed people tended to be more accurate when estimating time whereas non-depressed people tended to be less accurate. This finding, along with some of our other work, suggests that depression leads to more attention paid to time passing. Sometimes this might lead to a phenomenon known as ‘depressive realism’, though on other occasions time might seem to be moving more slowly than usual.”
In the study, volunteers, who were classified as mildly depressed or non-depressed, made estimates of the length of different time intervals of between two and sixty-five seconds. Overall, those volunteers who were mildly–depressed were more accurate in their time estimations.
Dr Msetfi noted that: “Time is a very important part of everyday experience, it flies when we are having fun or enjoying ourselves. One of the commonest experiences of depression is that people feel that time passes slowly and sometimes painfully. Our findings may help to shed a little light on how people with depression can be treated. People with depression are often encouraged to check themselves against reality, but maybe this timing skill can be harnessed to help in the treatment of mildly-depressed people. These findings may also link to successful mindfulness based treatments for depression which focus on encouraging present moment awareness.”
The paper, “Time perception and depressive realism: Judgement type, psychophysical functions and bias”, is published in PLOS ONE.
(Source: ul.ie)
Omega-3 removes ADHD symptoms
A new multidisciplinary study shows a clear connection between the intake of omega-3 fatty acids and a decline in ADHD symptoms in rats.
Researchers at the University of Oslo have observed the behaviour of rats and have analyzed biochemical processes in their brains. The results show a clear improvement in ADHD-related behaviour from supplements of omega-3 fatty acids, as well as a faster turnover of the signal substances dopamine, serotonin and glutamate in the nervous system. There are, however, clear sex differences: a better effect from omega-3 fatty acids is achieved in male rats than in female.
Unknown biology behind ADHD
Currently the psychiatric diagnosis ADHD (Attention Deficit/Hyperactivity Disorder) is purely based on behavioural criteria, while the molecular genetic background for the illness is largely unknown. The new findings indicate that ADHD has a biological component and that the intake of omega-3 may influence ADHD symptoms.
“In some research environments it is controversial to suggest that ADHD has something to do with biology. But we have without a doubt found molecular changes in the brain after rats with ADHD were given omega-3,” says Ivar Walaas, Professor of Biochemistry.
The fact that omega-3 can reduce ADHD behaviour in rats has also been indicated in previous international studies. What is unique about the study in question is a multidisciplinarity that has not previously been seen, with contributions from behavioural science in medicine as well as from psychology, nutritional science and biochemistry.
Hyperactive rats
The rats used in the study are called SHR rats – spontaneously hypertensive rats. Although this is primarily a common type of rat, random mutations in their genes have resulted in genetic damage that produces high blood pressure. It is therefore first and foremost blood-pressure researchers who have so far been interested in these rats.
However, the rats do not suffer from high blood pressure until they have reached puberty. Before that age they present totally different symptoms – namely hyperactivity, poor ability to concentrate and impulsiveness. It is exactly these three criteria that form the basis for making the ADHD diagnosis in humans. The animals also react to Ritalin, the central nervous system stimulant, in the same way as humans with ADHD: the hyperactive responses are stabilized. SHR rats are therefore increasingly used in research as a model for ADHD.
Supplements as early as the foetal stage
Researchers believe that omega-3 can have an effect from the very beginning of life. Omega-3 was therefore added to the food given to mother rats before they were impregnated, and this continued throughout their entire pregnancy and while they fed their young. The baby rats were also given omega-3 in their own food after they were separated from their mother at the age of 20 days. Another group of mother rats were given food that did not have omega-3 added, thus creating a control group of SHR offspring that had not been given these fatty acids at the foetal stage or later.
The researchers started to analyze the behaviour of the offspring some days after they were separated from the mother. They studied behaviour driven by reward as well as spontaneous behaviour. Substantial differences were noted for both types of behaviour between the rats that had been given the omega-3 supplement as foetuses and as baby rats and those that had not.
Rewards made male rats more concentrated
The reward-driven behaviour was such that the rats were allowed access to a drop of water each time they pressed an illuminated button. The ADHD rats that had not been given omega-3 could not concentrate on pressing the button, whereas the rats that had been brought up on omega-3 easily managed to hold their concentration for the seconds this takes and were able to enjoy a delicious drop of water as a reward.
Surprisingly enough, it was only male rats that showed an improvement in reward-driven behaviour. However, with regard to the rats’ spontaneous behavior, the same type of reduction in hyperactivity and attention difficulties was noted in both male and female rats that had been given the omega-3 supplement.
Changes in brain chemistry
Professor Walaas and his research group became involved in the study at this point in order to analyze the molecular processes in the rats’ brains.
The group analyzed the level of the chemical connections in the brain, the so-called neurotransmitters that transfer nerve impulses from one nerve cell to another. The researchers measured how much of the neurotransmitters such as dopamine, serotonin and glutamate was released and broken down within the nerve fibres. A key player in this work was Kine S. Dervola, PhD candidate, who reports clear sex differences in the turnover of the neurotransmitters – just as there had been in the reward-driven behaviour.
“We saw that the turnover of dopamine and serotonin took place much faster among the male rats that had been given omega-3 than among those that had not. For serotonin the turnover ratio was three times higher, and for dopamine it was just over two and a half times higher. These effects were not observed among the female rats. When we measured the turnover of glutamate, however, we saw that both sexes showed a small increase in turnover,” Ms Dervola tells us.
Transferrable to humans?
The researchers are cautious about drawing conclusions as to whether the results can be transferred to humans.
“In the first place there is of course a difference between rats and humans, and secondly the rats are sick at the outset. Thirdly the causes of ADHD in humans are in no way mapped sufficiently well. But the end result of what takes place in the brains of both rats and humans with ADHD is hyperactivity, poor ability to concentrate and impulsiveness,” says Professor Walaas, and concludes:
“Giving priority to basic research like this will greatly increase our detailed knowledge of ADHD.”
Reference:
Dervola, Kine-Susann Noren; Roberg, Bjørg Åse; Wøien, Grete; Bogen, Inger Lise; Sandvik, Torbjørn; Sagvolden, Terje; Drevon, Christian A, Espen B. Johansen and Sven Ivar Walaas (2012). Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behavior and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD. Behavioral and Brain Functions. ISSN 1744-9081. 8(56).
(Source: med.uio.no)
Receptor may aid spread of Alzheimer’s and Parkinson’s in brain
Scientists at Washington University School of Medicine in St. Louis have found a way that corrupted, disease-causing proteins spread in the brain, potentially contributing to Alzheimer’s disease, Parkinson’s disease and other brain-damaging disorders.
Image: An electron micrograph shows clumps of corrupted tau protein outside a nerve cell. Scientists have identified a receptor that lets these clumps into the cell, where the corruption can spread. Blocking this receptor with drugs may help treat Alzheimer’s, Parkinson’s and other disorders.
The research identifies a specific type of receptor and suggests that blocking it may aid treatment of theses illnesses. The receptors are called heparan sulfate proteoglycans (HSPGs).
“Many of the enzymes that create HSPGs or otherwise help them function are good targets for drug treatments,” said senior author Marc I. Diamond, MD, the David Clayson Professor of Neurology. “We ultimately should be able to hit these enzymes with drugs and potentially disrupt several neurodegenerative conditions.”
The study is available online in the Proceedings of the National Academy of Sciences.
Over the last decade, Diamond has gathered evidence that Alzheimer’s disease and other neurodegenerative diseases spread through the brain in a fashion similar to conditions such as mad cow disease, which are caused by misfolded proteins known as prions.
Proteins are long chains of amino acids that perform many basic biological functions. A protein’s abilities are partially determined by the way it folds into a 3-D shape. Prions are proteins that have become folded in a fashion that makes them harmful.
Prions spread across the brain by causing other copies of the same protein to misfold.
Among the most infamous prion diseases are mad cow disease, which rapidly destroys the brain in cows, and a similar, inherited condition in humans called Creutzfeldt-Jakob disease.
Diamond and his colleagues have shown that a part of nerve cells’ inner structure known as tau protein can misfold into a configuration called an amyloid. These corrupted versions of tau stick to each other in clumps within the cells. Like prions, the clumps spread from one cell to another, seeding further spread by causing copies of tau protein in the new cell to become amyloids.
In the new study, first author Brandon Holmes, an MD/PhD student, showed that HSPGs are essential for binding, internalizing and spreading clumps of tau. When he genetically disabled or chemically modified the HSPGs in cell cultures and in a mouse model, clumps of tau could not enter cells, thus inhibiting the spread of misfolded tau from cell to cell.
Holmes also found that HSPGs are essential for the cell-to-cell spread of corrupted forms of alpha-synuclein, a protein linked to Parkinson’s disease.
“This suggests that it may one day be possible to unify our understanding and treatment of two or more broad classes of neurodegenerative disease,” Diamond said.
“We’re now sorting through about 15 genes to determine which are the most essential for HSPGs’ interaction with tau,” Holmes said. “That will tell us which proteins to target with new drug treatments.”
(Source: news.wustl.edu)