Posts tagged neuroscience
Articles and news from the latest research reports.
Preschoolers Can Reflect on What They Don’t Know
Contrary to previous assumptions, researchers find that preschoolers are able to gauge the strength of their memories and make decisions based on their self-assessments. The study findings are published in Psychological Science, a journal of the Association for Psychological Science.
“Previously, developmental researchers assumed that preschoolers did not introspect much on their mental states, and were not able to reflect on their own uncertainty when problem solving,” says psychological scientist Emily Hembacher of the University of California, Davis, lead author of the study. “This is partly because young children are not usually able to tell us much about their own mental processes due to verbal limitations.”
In several previous studies in their lab, Hembacher and co-author Simona Ghetti observed that preschoolers reported feeling uncertain after giving wrong answers during tasks, suggesting the preschoolers were capable of metacognition — the ability to evaluate one’s own thoughts and mental states.
The researchers decided to examine preschoolers’ metacognition about their memories, given its importance for learning. They investigated whether kids could assess their confidence in their memories and use those assessments in deciding whether to exclude answers they had generated but were unsure of when given the option.
Eighty-one children ages 3, 4, and 5 participated in the study. The preschoolers viewed a series of drawings of various items, such as a piano or a balloon. Half of the images were presented once, and the other half were shown twice. Next, the children were presented with a pair of images: one they had seen, and a new one they had not seen. The children were instructed to pick which image they’d seen before in the previous task.
After making their choice, the preschoolers rated how confident they were that their choice was correct. They then sorted their answers into two boxes. One box was for the responses that children were confident about and wanted researchers to evaluate for a prize. The other one was for responses the children thought might be mistaken and that they didn’t want researchers to see.
The data revealed that only 4- and 5-year-olds reported being less confident in their incorrect than their correct memory responses. They were also more confident about images they’d seen twice, suggesting that they could distinguish between stronger and weaker memories. Older preschoolers were also more likely to decide whether they wanted researchers to see their answers based on their confidence level.
Although 3-year-olds didn’t display the same kind of metacognitive capability on individual responses, the data showed that 3-year-olds who had scored well reported higher confidence overall than kids who hadn’t scored as well.
When the researchers analyzed just the correct answers, they found that preschoolers of all ages sorted responses they weren’t as confident about to the box they didn’t want researchers to evaluate. So, while they may not be as advanced as their older peers, even children as young as 3 seem to display some ability to reflect on their own knowledge.
The findings contribute to research on the reliability of children’s eyewitness testimony in a court of law, and they carry important implications for educational practices.
“Previous emphasis on the development of metacognition during middle childhood has influenced education practices aimed at strengthening children’s monitoring and control of their own learning,” says Hembacher. “Now we know that some of these ideas may be adapted to meet preschoolers’ learning needs.”
(Source: psychologicalscience.org)
Brain waves show learning to read does not end in 4th grade, contrary to popular theory
Teachers-in-training have long been taught that fourth grade is when students stop learning to read and start reading to learn. But a new Dartmouth study in the journal Developmental Science tested the theory by analyzing brain waves and found that fourth-graders do not experience a change in automatic word processing, a crucial component of the reading shift theory. Instead, some types of word processing become automatic before fourth grade, while others don’t switch until after fifth.
The findings mean that teachers at all levels of elementary school must think of themselves as reading instructors, said the study’s author, Associate Professor of Education Donna Coch.
"Until now, we lacked neurological evidence about the supposed fourth-grade shift," said Coch, also principal investigator for Dartmouth’s Reading Brains Lab. "The theory developed from behavioral evidence, and as a result of it, some teachers in fifth and sixth grade have not thought of themselves as reading instructors. Now we can see from brain waves that students in those grades are still learning to process words automatically; their neurological reading system is not yet adult-like."
Automatic word processing is the brain’s ability to determine whether a group of symbols constitutes a word within milliseconds, without the brain’s owner realizing the process is taking place.
To test how automatic word processing develops, Coch placed electrode caps on the heads of third-, fourth-, and fifth-graders, as well as college students. She had her test subjects view a screen that displayed a mix of real English words (such as “bed”), pseudo-words (such as “bem”), strings of letters (such as “mbe”), and strings of meaningless symbols one at a time. The setup allowed her to see how the subjects’ brains reacted to each kind of stimulus within milliseconds. In other words, she could watch their automatic word processing.
Next, Coch gave the participants a written test, in which they were asked to circle the real words in a list that also contained pseudo-words, strings of letters, and strings of meaningless symbols. This task was designed to test the participants’ conscious word processing, a much slower procedure.
Interestingly, most of the 96 participants got a nearly perfect score on the written test, showing that their conscious brains knew the difference between words and non-words.
However, the electrode cap revealed that only the college students processed meaningless symbols differently than real words. The third-, fourth-, and fifth-graders’ brains reacted to the meaningless symbols the same way they reacted to common English words.
"This tells us that, at least through the fifth grade, even children who read well are letting stimuli into the neural word processing system that more mature readers do not," Coch said. "Their brains are processing strings of meaningless symbols as if they were words, perhaps in case they turn out to be real letters. In contrast, by college, students have learned not to process strings of meaningless symbols as words, saving their brains precious time and energy."
The phenomenon is evidence that young readers do not fully develop automatic word processing skills until after fifth grade, which contradicts the fourth-grade reading shift theory.
The brain waves also showed that the third-, fourth-, and fifth-graders processed real words, psuedowords, and letter strings similarly to college students, suggesting that some automatic word processing begins before the fourth grade, and even before the third grade, also contradicting the reading shift theory.
"There is value to the theory of the fourth grade shift in that it highlights how reading skills and abilities develop at different times," Coch said. "But the neural data suggest that teachers should not expect their fourth-graders, or even their fifth-graders, to be completely automatic, adult-like readers."
Stress tied to change in children’s gene expression related to emotion regulation, physical health
Children who have been abused or neglected early in life are at risk for developing both emotional and physical health problems. In a new study, scientists have found that maltreatment affects the way genes are activated, which has implications for children’s long-term development. Previous studies focused on how a particular child’s individual characteristics and genetics interacted with that child’s experiences in an effort to understand how health problems emerge. In the new study, researchers were able to measure the degree to which genes were turned “on” or “off” through a biochemical process called methylation. This new technique reveals the ways that nurture changes nature—that is, how our social experiences can change the underlying biology of our genes.
The study, from researchers at the University of Wisconsin, Madison, appears in the journal Child Development. Nearly 1 million children in the United States are neglected or abused every year.
The researchers found an association between the kind of parenting children had and a particular gene (called the glucocorticoid receptor gene) that’s responsible for crucial aspects of social functioning and health. Not all genes are active at all times. DNA methylation is one of several biochemical mechanisms that cells use to control whether genes are turned on or off. The researchers examined DNA methylation in the blood of 56 children ages 11 to 14. Half of the children had been physically abused.
They found that compared to the children who hadn’t been maltreated, the maltreated children had increased methylation on several sites of the glucocorticoid receptor gene, also known as NR3C1, echoing the findings of earlier studies of rodents. In this study, the effect occurred on the section of the gene that’s critical for nerve growth factor, which is an important part of healthy brain development.
There were no differences in the genes that the children were born with, the study found; instead, the differences were seen in the extent to which the genes had been turned on or off. “This link between early life stress and changes in genes may uncover how early childhood experiences get under the skin and confer lifelong risk,” notes Seth D. Pollak, professor of psychology and pediatrics at the University of Wisconsin, Madison, who directed the study.
Previous studies have shown that children who have experienced physical abuse, sexual abuse, and neglect are more likely to develop mood, anxiety, and aggressive disorders, as well as to have problems regulating their emotions. These problems, in turn, can disrupt relationships and affect school performance. Maltreated children are also at risk for chronic health problems such as cardiac disease and cancer. The current study helps explain why these childhood experiences can affect health years later.
The gene identified by the researchers affects the hypothalamic-pituitary-adrenal (HPA) axis in rodents. Disruptions of this system in the brain would make it difficult for people to regulate their emotional behavior and stress levels. Circulating through the body in the blood, this gene affects the immune system, leaving individuals less able to fight off germs and more vulnerable to illnesses.
"Our finding that children who were physically maltreated display a specific change to the glucocorticoid receptor gene could explain why abused children have more emotional difficulties as they age," according to Pollak. "They may have fewer glucocorticoid receptors in their brains, which would impair the brain’s stress-response system and result in problems regulating stress."
The findings have implications for designing more effective interventions for children, especially since studies of animals indicate that the effects of poor parenting on gene methylation may be reversible if caregiving improves. The study also adds to what we know about how child maltreatment relates to changes in the body and mind, findings that were summarized recently in an SRCD Social Policy Report by Sara R. Jaffee and Cindy W. Christian.
Researcher shows how stress hormones promote brain’s building of negative memories
When a person experiences a devastating loss or tragic event, why does every detail seem burned into memory whereas a host of positive experiences simply fade away?
It’s a bit more complicated than scientists originally thought, according to a study recently published in the journal Neuroscience by ASU researcher Sabrina Segal.
When people experience a traumatic event, the body releases two major stress hormones: norepinephrine and cortisol. Norepinephrine boosts heart rate and controls the fight-or-flight response, commonly rising when individuals feel threatened or experience highly emotional reactions. It is chemically similar to the hormone epinephrine – better known as adrenaline.
In the brain, norepinephrine in turn functions as a powerful neurotransmitter or chemical messenger that can enhance memory.
Research on cortisol has demonstrated that this hormone can also have a powerful effect on strengthening memories. However, studies in humans up until now have been inconclusive – with cortisol sometimes enhancing memory, while at other times having no effect.
A key factor in whether cortisol has an effect on strengthening certain memories may rely on activation of norepinephrine during learning, a finding previously reported in studies with rats.
In her study, Segal, an assistant research professor at the Institute for Interdisciplinary Salivary Bioscience Research at ASU, and her colleagues at the University of California-Irvine showed that human memory enhancement functions in a similar way.
Conducted in the laboratory of Larry Cahill at U.C. Irvine, Segal’s study included 39 women who viewed 144 images from the International Affective Picture Set. This set is a standardized picture set used by researchers to elicit a range of responses, from neutral to strong emotional reactions, upon view.
Segal and her colleagues gave each of the study’s subjects either a dose of hydrocortisone – to simulate stress – or a placebo just prior to viewing the picture set. Each woman then rated her feelings at the time she was viewing the image, in addition to giving saliva samples before and after. One week later, a surprise recall test was administered.
What Segal’s team found was that “negative experiences are more readily remembered when an event is traumatic enough to release cortisol after the event, and only if norepinephrine is released during or shortly after the event.”
“This study provides a key component to better understanding how traumatic memories may be strengthened in women,” Segal added, “because it suggests that if we can lower norepinephrine levels immediately following a traumatic event, we may be able to prevent this memory enhancing mechanism from occurring, regardless of how much cortisol is released following a traumatic event.”
Further studies are needed to explore to what extent the relationship between these two stress hormones differ depending on whether you are male or female, particularly because women are twice as likely to develop disorders from stress and trauma that affect memory, such as in Posttraumatic Stress Disorder (PTSD). In the meantime, the team’s findings are a first step toward a better understanding of neurobiological mechanisms that underlie traumatic disorders, such as PTSD.
(Image: Wikimedia Commons)
Schizophrenia’s genetic skyline rising
The largest genomic dragnet of any psychiatric disorder to date has unmasked 108 chromosomal sites harboring inherited variations in the genetic code linked to schizophrenia, 83 of which had not been previously reported. By contrast, the “skyline” of such suspect variants associated with the disorder contained only 5 significant peaks in 2011. By combining data from all available schizophrenia genetic samples, researchers supported by the National Institutes of Health powered the search for clues to the molecular basis of the disorder to a new level.
“While the suspect variation identified so far only explains only about 3.5 percent of the risk for schizophrenia, these results warrant exploring whether using such data to calculate an individual’s risk for developing the disorder might someday be useful in screening for preventive interventions,” explained Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health, one funder of the study. “Even based on these early predictors, people who score in the top 10 percent of risk may be up to 20-fold more prone to developing schizophrenia.”
The newfound genomic signals are not simply random sites of variation, say the researchers. They converge around pathways underlying the workings of processes involved in the disorder, such as communication between brain cells, learning and memory, cellular ion channels, immune function and a key medication target.
The Schizophrenia Working Group of the Psychiatric Genomic Consortium (PGC) reports on its genome-wide analysis of nearly 37,000 cases and more than 113,000 controls in the journal Nature, July 21, 2014. The NIMH-supported PGC represents more than 500 investigators at more than 80 research institutions in 25 countries.
Prior to the new study, schizophrenia genome-wide studies had identified only about 30 common gene variants associated with the disorder. Sample sizes in these studies were individually too small to detect many of the subtle effects on risk exerted by such widely shared versions of genes. The PGC investigators sought to maximize statistical power by re-analyzing not just published results, but all available raw data, published and unpublished. Their findings of 108 illness-associated genomic locations were winnowed from an initial pool of about 9.5 million variants.
A comparison of the combined study data with findings in an independent sample of cases and controls suggest that considerably more such associations of this type are likely to be uncovered with larger sample sizes, say the researchers.
There was an association confirmed with variation in the gene that codes for a receptor for the brain chemical messenger dopamine, which is known to be the target for antipsychotic medications used to treat schizophrenia. Yet evidence from the study supports the view that most variants associated with schizophrenia appear to exert their effects via the turning on and off of genes rather than through coding for proteins.
The study found a notable overlap between protein-related functions of some linked common variants and rare variants associated with schizophrenia in other studies. These included genes involved in communication between neurons via the chemical messenger glutamate, learning and memory, and the machinery controlling the influx of calcium into cells.
“The overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia,” say the researchers.
Among the strongest associations detected, as in in previous genome-wide genetic studies, was for variation in tissues involved in immune system function. Although the significance of this connection for the illness process remains a mystery, epidemiologic evidence has long hinted at possible immune system involvement in schizophrenia.
Findings confirm that it’s possible to develop risk profile scores based on schizophrenia-associated variants that may be useful in research – but for now aren’t ready to be used clinically as a predictive test, say the researchers.
They also note that the associated variations detected in the study may not themselves be the source of risk for schizophrenia. Rather, they may be signals indicating the presence of disease-causing variation nearby in a chromosomal region.
Researchers are following up with studies designed to pinpoint the specific sequences and genes that confer risk. The PGC is also typing genes in hundreds of thousands of people worldwide to enlarge the sample size, in hopes of detecting more genetic variation associated with mental disorders. Successful integration of data from several GWAS studies suggests that this approach would likely be transferrable to similar studies of other disorders, say the researchers.
“These results underscore that genetic programming affects the brain in tiny, incremental ways that can increase the risk for developing schizophrenia,” said Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “They also validate the strategy of examining both common and rare variation to understand this complex disorder.”
Researchers discover neuroprotective role of immune cell
A type of immune cell widely believed to exacerbate chronic adult brain diseases, such as Alzheimer’s disease and multiple sclerosis (MS), can actually protect the brain from traumatic brain injury (TBI) and may slow the progression of neurodegenerative diseases, according to Cleveland Clinic research published today in the online journal Nature Communications.
The research team, led by Bruce Trapp, PhD, Chair of the Department of Neurosciences at Cleveland Clinic’s Lerner Research Institute, found that microglia can help synchronize brain firing, which protects the brain from TBI and may help alleviate chronic neurological diseases. They provided the most detailed study and visual evidence of the mechanisms involved in that protection.
"Our findings suggest the innate immune system helps protect the brain after injury or during chronic disease, and this role should be further studied," Dr. Trapp said. "We could potentially harness the protective role of microglia to improve prognosis for patients with TBI and delay the progression of Alzheimer’s disease, MS, and stroke. The methods we developed will help us further understand mechanisms of neuroprotection."
Microglias are primary responders to the brain after injury or during illness. While researchers have long believed that activated microglia cause harmful inflammation that destroys healthy brain cells, some speculate a more protective role. Dr. Trapp’s team used an advanced technique called 3D electron microscopy to visualize the activation of microglia and subsequent events in animal models.
They found that when chemically activated, microglia migrate to inhibitory synapses, connections between brain cells that slow the firing of impulses. They dislodge the synapse (called “synaptic stripping”), thereby increasing neuronal firing and leading to a cascade of events that enhance survival of brain cells.
Trapp is internationally known for his work on mechanisms of neurodegeneration and repair in multiple sclerosis. His past research has included investigation of the cause of neurological disability in MS patients, cellular mechanisms of brain repair in neurodegenerative diseases, and the molecular biology of myelination in the central and peripheral nervous systems.
(Source: eurekalert.org)
Brain imaging study examines second-language learning skills
With enough practice, some learners of a second language can process their new language as well as native speakers, research at the University of Kansas shows.
(Credit: bigstockphoto)
Using brain imaging, a trio of KU researchers was able to examine to the millisecond how the brain processes a second language. They then compared their findings with their previous results for native speakers and saw both followed similar patterns.
The research by Robert Fiorentino and Alison Gabriele, both associate professors in the linguistics department, and José Alemán Bañón, a former KU graduate student who is now a postdoctoral researcher at the University of Reading in the United Kingdom, was published this month in the journal Second Language Research.
For years, linguists have debated whether second-language learners would ever resemble native speakers in their ability to process language properties that differ between the first and second language, such as gender agreement, which is a property of Spanish but not English. In Spanish, all nouns are categorized as masculine or feminine, and various elements in the sentence, such as adjectives, need to carry the gender feature of the noun as well.
Some researchers argued that even those who spoke a second language with a high level of accuracy were using a qualitatively different mechanism than native speakers.
“We realized that these different theories proposing that either second-language learners use the same mechanism, or a different mechanism could actually be teased apart by using brain-imaging techniques,” Gabriele said.
The team studied 26 high-level Spanish speakers who hadn’t learned to speak Spanish until after age 11 and grew up with English as the majority language. The speakers used Spanish on a daily basis and had spent an average of a year and a half in a Spanish-speaking country.
They were compared with 24 native speakers, who were raised in Spanish-speaking countries and stayed in their home country until age 17.
To measure language processing as it happens, the team used a method known as electroencephalography (EEG), which uses an array of electrodes placed on the scalp to detect patterns of brain activity with high accuracy in timing.
Once hooked up to the EEG, the test subjects were asked to read sentences, some of which had grammatical errors in either number agreement or gender agreement.
The researchers then compared the results of the second-language learners to native speakers. They found that the highly proficient second-language speakers showed the same patterns of brain activity as native speakers when processing grammatical violations in sentences.
“We show that the learners’ brain activity looks qualitatively similar to that of native speakers, suggesting that they are using the same mechanisms,” Fiorentino said.
The study highlights the brain’s plasticity and its ability to acquire a new complex system even in adulthood.
“A lot of researchers have argued that there is some sort of language learning mechanism that might atrophy over the life span, particularly before puberty. And, we certainly have a lot of evidence that it is difficult to process your second language at nativelike levels and you have to go through quite a bit of effort to find people who can,” Gabriele said. “But I think what this paper shows is that it is possible.”
Gabriele and Fiorentino are working on a second phase of the research, studying how the brain processes a second language at the initial stages of exposure. Their preliminary results suggest that properties that are shared between the first and second language show patterns of brain activity that are very similar in learners and native speakers. This suggests that learners build on the representation for language that is already in place when learning a second language.
(Source: news.ku.edu)
Low Strength Brain Stimulation May Be Effective for Depression
Brain stimulation treatments, like electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), are often effective for the treatment of depression. Like antidepressant medications, however, they typically have a delayed onset. For example, a patient may receive several weeks of regular ECT treatments before a full response is achieved.
Thus, there is an impetus to develop antidepressant treatments that act to rapidly improve mood.
Low field magnetic stimulation (LFMS) is one such potential new treatment with rapid mood-elevating effects, as reported by researchers at Harvard Medical School and Weill Cornell Medical College.
"LFMS is unlike any current treatment. It uses magnetic fields that are a fraction of the strength but at higher frequency than the electromagnetic fields used in TMS and ECT," explained first author Dr. Michael Rohan.
Indeed, the potential antidepressant properties of LFMS were discovered accidentally, while researchers were conducting an imaging study in healthy volunteers. This led Rohan and his colleagues to conduct a preliminary study in which they identified the imaging parameters that seemed to be causing the antidepressant effect.
They then designed and constructed a portable LFMS device, which delivers a low strength, high frequency, electromagnetic field waveform to the brain. The next step was to test the device in depressed patients, the results of which are published in the current issue of Biological Psychiatry.
A total of 63 currently depressed patients, diagnosed with either major depressive disorder or bipolar disorder, participated in the study and were randomized to receive a single 20-minute treatment of real LFMS or sham LFMS, where the device was on but the electromagnetic fields were inactive. Since neither the patients nor the researchers knew which treatment each person actually received, the true effect of the LFMS could be measured.
An immediate and substantial improvement in mood was observed in the patients who received real LFMS, compared to those who received the sham treatment. There were no reported side effects.
This finding suggests that LFMS may have the potential to provide immediate relief of depressed mood, perhaps even in emergency situations. It also confirms the success of the device’s design.
"The idea that weak electrical stimulation of the brain could produce beneficial effects on depression symptoms is somewhat surprising," said Dr. John Krystal, Editor of Biological Psychiatry. “Yet the data make a compelling case that this safe approach deserves further study.”
Rohan confirmed that additional research is underway to find the best parameters for LFMS use in the clinical treatment of depression. Further research will also be necessary to evaluate the effects of multiple compared to single treatments, and how long the antidepressant effects last following treatment.
Rigid connections: Molecular basis of age-related memory loss explained
From telephone numbers to foreign vocabulary, our brains hold a seemingly endless supply of information. However, as we are getting older, our ability to learn and remember new things declines. A team of scientists around Associate Prof Dr Antonio Del Sol Mesa from the Luxembourg Centre for Systems Biomedicine of the University of Luxembourg and Dr Ronald van Kesteren of the VU University Amsterdam have identified the molecular mechanisms of this cognitive decline using latest high-throughput proteomics and statistical methods.
The results were published this week in the prestigious scientific journal “Molecular and Cellular Proteomics”.
Brain cells undergo chemical and structural changes, when information is written into our memory or recalled afterwards. Particularly, the number and the strength of connections between nerve cells, the so-called synapses, changes. To investigate why learning becomes more difficult even during healthy ageing, the scientists looked at the molecular composition of brain connections in healthy mice of 20 to 100 weeks of age. This corresponds to a period from puberty until retirement in humans. “Amazingly, there was only one group of four proteins of the so-called extracellular matrix which increased strongly with age. The rest stayed more or less the same,” says Prof Dr Antonio del Sol Mesa from the Luxembourg Centre for Systems Biomedicine.
The extracellular matrix is a mesh right at the connections between brain cells. A healthy amount of these proteins ensures a balance between stability and flexibility of synapses and is vital for learning and memory. “An increase of these proteins with age makes the connections between brain cells more rigid which lowers their ability to adapt to new situations. Learning gets difficult, memory slows down,” Dr Ronald van Kesteren of the VU University Amsterdam elaborates.
In addition, the researchers not only looked at the individual molecules but also analysed the whole picture using a systems biology approach. Here they described the interplay between molecules as networks that together tightly control the amount of individual molecules and their interactions. “A healthy network keeps all molecules in the right level for proper functioning. In older mice we found, however, that the overall molecular composition is more variable compared to younger animals. This shows that the network is losing its control and can be more easily disturbed when we age,” Prof Dr Antonio del Sol Mesa explains. According to the researchers this makes the brain more susceptible to diseases.
Hence, this insight into the normal aging process could also help in the future to better understand complex neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Chemical compounds that modulate the extracellular matrix might be promising new treatments for learning disorders and memory loss.
Study finds potential genetic link between epilepsy and neurodegenerative disorders
A recent scientific discovery showed that mutations in prickle genes cause epilepsy, which in humans is a brain disorder characterized by repeated seizures over time. However, the mechanism responsible for generating prickle-associated seizures was unknown.
A new University of Iowa study, published online July 14 in the Proceedings of the National Academy of Sciences, reveals a novel pathway in the pathophysiology of epilepsy. UI researchers have identified the basic cellular mechanism that goes awry in prickle mutant flies, leading to the epilepsy-like seizures.
“This is to our knowledge the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport,” says John Manak, senior author and associate professor of biology in the College of Liberal Arts and Sciences and pediatrics in the Carver College of Medicine.
Seizure suppression in flies
A neuron has an axon (nerve fiber) that projects from the cell body to different neurons, muscles, and glands. Information is transmitted along the axon to help a neuron function properly.
Manak and his fellow researchers show that seizure-prone prickle mutant flies have behavioral defects (such as uncoordinated gait) and electrophysiological defects (problems in the electrical properties of biological cells) similar to other fly mutants used to study seizures. The researchers also show that altering the balance of two forms of the prickle gene disrupts neural information flow and causes epilepsy.
Further, they demonstrate that reducing either of two motor proteins responsible for directional movement of vesicles (small organelles within a cell that contain biologically important molecules) along tracks of structural proteins in axons can suppress the seizures.
“The reduction of either of two motor proteins, called Kinesins, fully suppressed the seizures in the prickle mutant flies,” says Manak, faculty member in the Interdisciplinary Graduate Programs in Genetics, Molecular and Cellular Biology, and Health Informatics. “We were able to use two independent assays to show that we could suppress the seizures, effectively ‘curing’ the flies of their epileptic behaviors.”
Genetic link between epilepsy and Alzheimer’s
This new epilepsy pathway was previously shown to be involved in neurodegenerative diseases, including Alzheimer’s and Parkinson’s.
Manak and his colleagues note that two Alzheimer’s-associated proteins, amyloid precursor protein and presenilin, are components of the same vesicle, and mutations in the genes encoding these proteins in flies affect vesicle transport in ways that are strikingly similar to how transport is impacted in prickle mutants.
“We are particularly excited because we may have stumbled upon one of the key genetic links between epilepsy and Alzheimer’s, since both disorders are converging on the same pathway,” Manak says. “This is not such a crazy idea. In fact, Dr. Jeff Noebels, a leading epilepsy researcher, has presented compelling evidence suggesting a link between these disorders. Indeed, patients with inherited forms of Alzheimer’s disease also present with epilepsy, and this has been documented in a number of published studies.”
Manak adds, “If this connection is real, then drugs that have been developed to treat neurodegenerative disorders could potentially be screened for anti-seizure properties, and vice versa.”
Manak’s future research will involve treating seizure-prone flies with such drugs to see if he can suppress their seizures.
(Source: now.uiowa.edu)