Posts tagged science
Articles and news from the latest research reports.
Variations in Neuronal Networks Could Explain Traumatic Brain Injury Outcomes
A team of researchers at the Neuroscience Institute at Georgia State University has discovered that hidden differences in the properties of neural circuits can account for whether animals are behaviorally susceptible to brain injury. These results could have implications for the treatment of brain trauma.
People vary in their responses to stroke and trauma, which impedes the ability of physicians to predict patient outcomes. Damage to the brain and nervous system can lead to severe disabilities, including epilepsy and cognitive impairment.
If doctors could predict outcomes with greater accuracy, patients might benefit from more tailored treatments. Unfortunately, the complexity of the human brain hinders efforts to explain why similar brain damage can affect each person differently.
The researchers used a unique research animal, a sea slug called Tritonia diomedea, to study this question. This animal was used because unlike humans, it has a small number of neurons and its behavior is simple. Despite this simplicity, the animals varied in how neurons were connected.
Under normal conditions, this variability did not matter to the animals’ behavior, but when a major pathway in the brain was severed, some of the animals showed little behavioral deficit, while others could not produce the behavior being studied. Remarkably, the researchers could artificially rewire the neural circuit using computer-generated connections and make animals susceptible or invulnerable to the injury.
“This study is important in light of the current Obama BRAIN initiative, which seeks to map all of the connections in the human brain,” said Georgia State professor, Paul Katz, who led the research project. “it shows that even in a simple brain, small differences that have no effect under normal conditions, have major implications when the nervous system is challenged by injury or trauma.”
Results of this study were published in the most recent edition of the journal eLife. The lead author on the study, Dr. Akira Sakurai, made this discovery in the course of doing basic research. He was assisted by Ph.D. student Arianna Tamvacakis from Dr. Katz’s lab.
(Source: news.gsu.edu)
(Image caption: In brain cancer cells, the protein PARC plays a key role in long-term cell survival. In both images, the red represents the protein cytochrome c, which is released when mitochondria are damaged and trigger apoptosis – cell suicide. At left, injured brain cancer cells exhibit little cytochrome c; they use the protein PARC to degrade the released cytochrome c, allowing the cancer cells to survive. At right, when researchers reduced PARC, cytochrome c accumulated, allowing apoptosis to carry on)
Neurons, brain cancer cells require the same little-known protein for long-term survival
Researchers at the UNC School of Medicine have discovered that the protein PARC/CUL9 helps neurons and brain cancer cells override the biochemical mechanisms that lead to cell death in most other cells. In neurons, long-term survival allows for proper brain function as we age. In brain cancer cells, though, long-term survival contributes to tumor growth and the spread of the disease.
These results, published in the journal Science Signaling, not only identify a previously unknown mechanism used by neurons for their much-needed survival, but show that brain cancer cells hijack the same mechanism for their own survival.
The discovery will lead to new investigations of brain cancer treatments and provides insight into Parkinson’s disease, including a potential new research tool for scientists.
“PARC is very similar to Parkin, a protein that’s mutated in Parkinson’s disease,” said Mohanish Deshmukh, PhD, a professor of cell biology and physiology and senior author of the Science Signaling paper. “We think they might work in tandem to protect neurons.”
If so, researchers can investigate the interplay between these proteins to create better drugs to treat the second-most prevalent neurodegenerative disease after Alzheimer’s disease.
Vivian Gama, PhD, a postdoctoral fellow in Deshmukh’s lab, led the experiments in cell cultures and animal models. First, she used external stimuli to promote the damage of mitochondria – the energy sources for cells. In most cell types, when mitochondria are damaged, they release a protein called cytochrome c, which triggers a cascade of biochemical steps that end in cell death – a process known as apoptosis.
Working with neurons, though, Gama found that the protein PARC/CUL9 blocked this process; it degraded cytochrome c, halted apoptosis, and allowed for long-term cell survival. “In this setting, we want PARC to do that because we want neurons to survive as long as possible,” said Gama, first author of the Science Signaling paper.
Deshmukh, a member of the UNC Neuroscience Center and the UNC Lineberger Comprehensive Cancer Center, said, “In Parkinson’s disease, we know that Parkin targets damaged mitochondria for degradation. However, exactly what happens to the proteins, such as cytochrome c, that are released from the damaged mitochondria has been unknown. Now, we think PARC plays a role in this process.”
Deshmukh and Gama’s work could lead to an alternative way to study Parkinson’s disease. Other researchers have created mouse models that lack the Parkin gene, but Gama said these models don’t have many of the hallmark symptoms that human patients have, making the model less than desirable for researchers. “Our hypothesis is that in the absence of Parkin, PARC still does the job,” Gama said, “as it may allow cells to survive.”
Gama and Deshmukh are now creating a model that lacks both the Parkin and PARC genes.
They will also investigate PARC as a target for cancer treatment.
“We tested several cancer cell lines and found that PARC degrades cytochrome c in medulloblastoma, a cancer of the central nervous system and in neuroblastoma, a cancer of the peripheral nervous system,” Gama said. “Not all cytochrome c is degraded; there are likely other factors involved. But PARC is an important player.”
When Gama and colleagues triggered the apoptotic process in brain cancer cells, they found that PARC allowed the cells to survive. When PARC was inhibited, the cells were more vulnerable to stress and damage, which means they could be more vulnerable to compounds aimed at destroying them.
Deshmukh said, “We show that brain cancer cells co-opt PARC to bypass apoptosis in the same way that neurons do and for the exact same purpose.”
Mutation stops worms from getting drunk
Neuroscientists at The University of Texas at Austin have generated mutant worms that do not get intoxicated by alcohol, a result that could lead to new drugs to treat the symptoms of people going through alcohol withdrawal.
The scientists accomplished this feat by inserting a modified human alcohol target into the worms, as reported this week in The Journal of Neuroscience.
"This is the first example of altering a human alcohol target to prevent intoxication in an animal," says corresponding author, Jon Pierce-Shimomura, assistant professor in the university’s College of Natural Sciences and Waggoner Center for Alcohol and Addiction Research.
An alcohol target is any neuronal molecule that binds alcohol, of which there are many.
One important aspect of this modified alcohol target, a neuronal channel called the BK channel, is that the mutation only affects its response to alcohol. The BK channel typically regulates many important functions including activity of neurons, blood vessels, the respiratory tract and bladder. The alcohol-insensitive mutation does not disrupt these functions at all.
"We got pretty lucky and found a way to make the channel insensitive to alcohol without affecting its normal function," says Pierce-Shimomura.
The scientists believe the research has potential application for treating people addicted to alcohol.
"Our findings provide exciting evidence that future pharmaceuticals might aim at this portion of the alcohol target to prevent problems in alcohol abuse disorders," says Pierce-Shimomura. "However, it remains to be seen which aspects of these disorders would benefit."
Unlike drugs such as cocaine, which have a specific target in the nervous system, the effects of alcohol on the body are complex and have many targets across the brain. The various other aspects of alcohol addiction, such as tolerance, craving and the symptoms of withdrawal, may be influenced by different alcohol targets.
The worms used in the study, Caenorhabditis elegans, model intoxication well. Alcohol causes the worms to slow their crawling with less wriggling from side to side. The intoxicated worms also stop laying eggs, which build up in their bodies and can be easily counted.
Unfortunately, C. elegans are not as ideal for studying the other areas of alcohol addiction, but mice make an excellent model. The modified human BK channel used in the study, which is based on a mutation discovered by lead author and graduate student Scott Davis, could be inserted into mice. These modified mice would allow scientists to investigate whether this particular alcohol target also affects tolerance, craving and other symptoms relevant to humans.
Pierce-Shimomura speculated that their research could even be used to develop a ‘James Bond’ drug someday, which would enable a spy to drink his opponent under the table, without getting drunk himself. Such a drug could potentially be used to treat alcoholics, since it would counteract the intoxicating and potentially addicting effects of the alcohol.
Transplantation of healthy new brain cells reverses learning and memory loss in Alzheimer’s disease model
A new study from the Gladstone Institutes has revealed a way to alleviate the learning and memory deficits caused by apoE4, the most important genetic risk factor for Alzheimer’s disease, improving cognition to normal levels in aged mice.
In the study, which was conducted in collaboration with researchers at UC San Francisco and published today in the Journal of Neuroscience, scientists transplanted inhibitory neuron progenitors—early-stage brain cells that have the capacity to develop into mature inhibitory neurons—into two mouse models of Alzheimer’s disease, apoE4 or apoE4 with accumulation of amyloid beta, another major contributor to Alzheimer’s. The transplants helped to replenish the brain by replacing cells lost due to apoE4, regulating brain activity and improving learning and memory abilities.
“This is the first time transplantation of inhibitory neuron progenitors has been used in aged Alzheimer’s disease models,” said first author Leslie Tong, a graduate student at the Gladstone Institutes and UCSF. “Working with older animals can be challenging from a technical standpoint, and it was amazing to see that the cells not only survived but affected activity and behavior.”
The success of the treatment in older mice, which corresponded to late adulthood in humans, is particularly important, as this would be the age that would be targeted were this method ever to be used therapeutically in people.
“This is a very important proof of concept study,” said senior author Yadong Huang, MD, PhD, an associate investigator at Gladstone Institutes and associate professor of neurology and pathology at UCSF. “The fact that we see a functional integration of these cells into the hippocampal circuitry and a complete rescue of learning and memory deficits in an aged model of Alzheimer’s disease is very exciting.”
A balance of excitatory and inhibitory activity in the brain is essential for normal function. However, in the apoE4 model of Alzheimer’s disease—a genetic risk factor that is carried by approximately 25% of the population and is involved in 60-75% of all Alzheimer’s cases—this balance gets disrupted due to a decline in inhibitory regulator cells that are essential in maintaining normal brain activity. The hippocampus, an important memory center in the brain, is particularly affected by this loss of inhibitory neurons, resulting in an increase in network activation that is thought to contribute to the learning and memory deficits characteristic of Alzheimer’s disease. The accumulation of amyloid beta in the brain has also been linked to this imbalance between excitatory and inhibitory activity in the brain.
In the current study, the researchers hoped that by grafting inhibitory neuron progenitors into the hippocampus of aged apoE4 mice, they would be able to combat these effects, replacing the lost cells and restoring normal function to the area. Remarkably, these new inhibitory neurons survived in the hippocampus, enhancing inhibitory signaling and rescuing impairments in learning and memory.
In addition, when these inhibitory progenitor cells were transplanted into apoE4 mice with an accumulation of amyloid beta, prior deficits were alleviated. However, the new inhibitory neurons did not affect amyloid beta levels, suggesting that the cognitive enhancement did not occur as a result of amyloid clearance, and amyloid did not impair the integration of the transplant.
According to Dr. Huang, the potential implications for these findings extend beyond the current methods used. “Stem cell therapy in humans is still a long way off. However, this study tells us that if there is any way we can enhance inhibitory neuron function in the hippocampus, like through the development of small molecule compounds, it may be beneficial for Alzheimer disease patients.”
(Source: gladstoneinstitutes.org)
Months before their first words, babies’ brains rehearse speech mechanics
Infants can tell the difference between sounds of all languages until about 8 months of age when their brains start to focus only on the sounds they hear around them. It’s been unclear how this transition occurs, but social interactions and caregivers’ use of exaggerated “parentese” style of speech seem to help.
University of Washington research in 7- and 11-month-old infants shows that speech sounds stimulate areas of the brain that coordinate and plan motor movements for speech.
The study, published July 14 in the Proceedings of the National Academy of Sciences, suggests that baby brains start laying down the groundwork of how to form words long before they actually begin to speak, and this may affect the developmental transition.
“Most babies babble by 7 months, but don’t utter their first words until after their first birthdays,” said lead author Patricia Kuhl, who is the co-director of the UW’s Institute for Learning and Brain Sciences. “Finding activation in motor areas of the brain when infants are simply listening is significant, because it means the baby brain is engaged in trying to talk back right from the start and suggests that 7-month-olds’ brains are already trying to figure out how to make the right movements that will produce words.”
Kuhl and her research team believe this practice at motor planning contributes to the transition when infants become more sensitive to their native language.
The results emphasize the importance of talking to kids during social interactions even if they aren’t talking back yet.
“Hearing us talk exercises the action areas of infants’ brains, going beyond what we thought happens when we talk to them,” Kuhl said. “Infants’ brains are preparing them to act on the world by practicing how to speak before they actually say a word.”
In the experiment, infants sat in a brain scanner that measures brain activation through a noninvasive technique called magnetoencephalography. Nicknamed MEG, the brain scanner resembles an egg-shaped vintage hair dryer and is completely safe for infants. The Institute for Learning and Brain Sciences was the first in the world to use such a tool to study babies while they engaged in a task.
The babies, 57 7- and 11- or 12-month-olds, each listened to a series of native and foreign language syllables such as “da” and “ta” as researchers recorded brain responses. They listened to sounds in English and in Spanish.
The researchers observed brain activity in an auditory area of the brain called the superior temporal gyrus, as well as in Broca’s area and the cerebellum, cortical regions responsible for planning the motor movements required for producing speech.
This pattern of brain activation occurred for sounds in the 7-month-olds’ native language (English) as well as in a non-native language (Spanish), showing that at this early age infants are responding to all speech sounds, whether or not they have heard the sounds before.
In the older infants, brain activation was different. By 11-12 months, infants’ brains increase motor activation to the non-native speech sounds relative to native speech, which the researchers interpret as showing that it takes more effort for the baby brain to predict which movements create non-native speech. This reflects an effect of experience between 7 and 11 months, and suggests that activation in motor brain areas is contributing to the transition in early speech perception.
The study has social implications, suggesting that the slow and exaggerated parentese speech – “Hiiiii! How are youuuuu?” – may actually prompt infants to try to synthesize utterances themselves and imitate what they heard, uttering something like “Ahhh bah bah baaah.”
“Parentese is very exaggerated, and when infants hear it, their brains may find it easier to model the motor movements necessary to speak,” Kuhl said.
Beneath the Surface: What Zebrafish Can Tell Us About Anxiety
The right tool for the job is important. A surgeon wouldn’t use a chainsaw when a scalpel offers more control. But sometimes the best treatments available aren’t precise. For example, anxiety medications available today are too blunt in how they target the brain, according to Ian Woods, assistant professor of biochemistry at Ithaca College.
“If you look at current treatments for anxiety disorders, the approach is a bit like taking a sledgehammer to a mosquito,” he said. “The treatments may work for anxiety, but they can have a lot of side effects.”
Woods researches how genetics influence responses to stimuli that can trigger anxiety, and he’s using zebrafish — a tropical member of the minnow family named for the black stripes on their bodies — to do so. He and his team of student researchers examine how fish with tweaked genes respond to different triggers compared to unmodified fish. The work could someday lead to better, more nuanced medications for anxiety disorders.
Zebrafish make ideal test subjects for several reasons. The embryos are transparent and develop outside the mother’s body, making it easy for Woods and his team to observe their growth under a microscope. They develop rapidly, are easy to care for and easy to breed in large quantities.
Specifically, Woods is looking at neuropeptides, which are the chemical messengers between brain cells. Different neuropeptides deliver different messages, which in turn produce different behaviors.
“Fish have the same neuropeptides as humans, and they mostly do the same things in the brain,” Woods said. “We can never faithfully model a complex human behavior like anxiety, but when we’re trying to figure out how the brain works, it’s useful to see inside a fish.”
Woods and his team isolate specific genes to disrupt, amplify, alter or replace, then analyze the movements of the modified fish with the aid of a computerized camera system. They examine responses to stimuli such as slight changes in water temperature, decreases in light intensity, or mild chemical irritants such as mustard oil.
“By observing the ensuing behavioral changes in the fish, we know how that replaced gene changed the message in the brain,” Woods explained. For example, fish exhibiting anxiety-like behaviors might hug the walls of the tank, while the rest will swim toward the middle. It’s not unlike social experiments in which the room temperature is raised gradually to see how human occupants will react.
“Genes typically don’t cause the anxiety,” Woods said. “But they can make organisms more susceptible to environmental triggers that might elicit what we’d call an anxious behavior.”
Anxiety disorders are the most common mental illness in the United States; over 40 million Americans suffer from some type in their lifetimes. But medications can be overprescribed and abused. For example, emergency room visits related to the use of Xanax and related drugs doubled from 2005 to 2011, according to the U.S. Substance Abuse and Mental Health Services Administration.
“Noisy” Memory in Schizophrenia
The inability to ignore irrelevant stimuli underlies the impaired working memory and cognition often experienced by individuals diagnosed with schizophrenia, reports a new study in the current issue of Biological Psychiatry.
Our brains are usually good at focusing on the information that we are trying to learn and filtering out the “noise” or thoughts that aren’t relevant. However, memory impairment in schizophrenia may be related in part to a problem with this filtering process, which Dr. Teal Eich at Columbia University and her colleagues studied.
“Our assumption was that understanding the impairments in the component processes of working memory – the ability to hold and manipulate information in the mind – among patients with schizophrenia could be fundamental to understanding not only cognitive function in the disorder, which is widespread and has debilitating consequences, but also the disorder itself,” Eich explained.
The researchers recruited patients with schizophrenia and a control group of healthy volunteers to complete an item recognition task in the laboratory while undergoing a functional magnetic resonance imaging scan. In particular, they focused on analyzing potential activation differences in the ventro-lateral prefrontal cortex (VLPFC), a region of the brain implicated in working memory.
The design of the task allowed for the assessment of the various components of working memory: 1) maintaining the memory itself, 2) inhibiting or ignoring irrelevant information, and 3) during memory retrieval, controlling the interference of irrelevant information.
While simply maintaining the memory, both groups showed a similar degree of activation in the VLPFC. During the inhibition phase, VLPFC activity is expected to decrease, which was indeed observed in the healthy group, but not in the patients. Finally, during interference control, patients performed worse and showed increased VLPFC activation compared to the healthy volunteers. Overall, the patients showed altered VLPFC functioning and significant impairments in their ability to control working memory.
“Our findings show that these patients have a specific deficit in inhibiting information in working memory, leading to impaired distinctions between relevant and irrelevant thoughts,” said Eich. “This result may provide valuable insights into the potential brain mechanisms underlying the reasons why these affected individuals are unable to control or put out of mind certain thoughts or ideas.”
This study adds to a growing literature suggesting that cognitive functions require both the activation of one set of regions and the inhibition of others. The failure to suppress activation may be just as disruptive to cortical functions as deficits in cortical activation.
Many years ago, the pioneering scientist Patricia Goldman-Rakic and her colleagues showed that the inhibition of regional prefrontal cortical activity was dependent upon the integrity of the GABA (gamma-aminobutyric acid) system in the brain, a chemical system with abnormalities associated with schizophrenia.
“We need to determine whether the cortical inhibitory deficits described in this study can be attributed to particular brain chemical signaling abnormalities,” said Dr. John Krystal, Editor of Biological Psychiatry. “If so, this type of study could be used to guide therapeutic strategies to enhance working memory function.”
(Source: elsevier.com)
Can Games, Puzzles Keep Aging Minds Sharp?
Older adults who enjoy mentally stimulating games may have bigger brains and sharper thinking skills than their peers, new research suggests.
The study looked at the connection between playing games such as puzzles, crosswords, cards and checkers and mental acuity for adults in their 50s and 60s.
Researchers found that people who played those games at least every other day performed better on tests of memory and other mental functions. And, based on MRI scans, they had greater tissue mass in brain areas involved in memory.
(Image: Alamy)
Older adults nearly twice as likely to have memories affected by environmental distractions
Older people are nearly twice as likely as their younger counterparts to have their memory and cognitive processes impaired by environmental distractions (such as irrelevant speech or written words presented along with target stimuli), according to a new study from psychologists at Rice University and Johns Hopkins University School of Medicine. Whereas other studies had found that older adults are distracted by memories of prior similar events, this was the first study to convincingly demonstrate across several tasks an impairment from environmental distractions.
“Cognitive Declines in Healthy Aging: Evidence from Multiple Aspects of Interference Resolution” appeared in a recent edition of Psychology and Aging. The study supported previous research that showed memory accuracy and the speed of cognitive processing declines with age. It also revealed that older people were at least twice as likely as younger to have irrelevant memories intrude during memory recall and also showed twice as much slowing in cognitive processing in the presence of distracting information in the environment.
The study included 102 people between the ages of 18 and 32 (average age of 21) and 60 people between the ages of 64 and 82 (average age of 71) who participated in a series of memory and cognitive tasks.
For example, when the participants were tested on remembering lists of words, individuals in the young test group remembered words on the list with an average accuracy of 81 percent; in comparison, the old test group’s accuracy was only 67 percent. When irrelevant words were introduced that were to be ignored, the young test group’s accuracy dropped to 74 percent, but the accuracy of the old test group’s performance dropped to 46 percent.
“Almost any type of memory test administered reveals a decline in memory from the age of 25 on,” said Randi Martin, the Elma W. Schneider Professor of Psychology at Rice and the study’s co-author. “However, this is the first study to convincingly demonstrate the impact of environmental interference on processing having a greater impact on older than younger adults.”
Martin hopes that the research will encourage further research of how the brain is affected by environmental distractions.
“From our perspective of studying neuroplasticity (the brain’s ability to reorganize itself after traumatic injury or neurological disorders) and testing patients with brain damage, this research is very important,” Martin said. “The tests used in this study are important tools in determining how the brain is affected by environmental interference, which is critical information in treating neurological disorders, including stroke and traumatic brain injuries.”
(Source: news.rice.edu)
US Alzheimer’s Rate Seems to Be Dropping
The rate of Alzheimer’s disease and other dementias is falling in the United States and some other rich countries — good news about an epidemic that is still growing simply because more people are living to an old age, new studies show.
An American over age 60 today has a 44 percent lower chance of developing dementia than a similar-aged person did roughly 30 years ago, the longest study of these trends in the U.S. concluded.
Dementia rates also are down in Germany, a study there found.
"For an individual, the actual risk of dementia seems to have declined," probably due to more education and control of health factors such as cholesterol and blood pressure, said Dr. Kenneth Langa. He is a University of Michigan expert on aging who discussed the studies Tuesday at the Alzheimer’s Association International Conference in Copenhagen.
The opposite is occurring in some poor countries that have lagged on education and health, where dementia seems to be rising.
More than 5.4 million Americans and 35 million people worldwide have Alzheimer’s, the most common form of dementia. It has no cure and current drugs only temporarily ease symptoms.
A drop in rates is a silver lining in the so-called silver tsunami — the expected wave of age-related health problems from an older population. Alzheimer’s will remain a major public health issue, but countries where rates are dropping may be able to lower current projections for spending and needed services, experts said.
Recent studies from the Netherlands, Sweden and England have suggested a decline, and the new research extends this look to some other parts of the world.
(Image: Thinkstock)