Posts tagged neuroscience
Articles and news from the latest research reports.
We are thrilled to draw your attention on the upcoming Brainhack 2013, which is being held from October 23-26 at the Centre International d’Études Pédagogiques, Sèvres, France (just outside of Paris).
Brainhack 2013 is a unique workshop with the goals of fostering interdisciplinary collaboration and open neuroscience. The structure builds from the concepts of an unconference and hackathon: The term “unconference” refers to the fact that most of the content will be dynamically created by the participants — a “hackathon” is an event where participants collaborate
intensively on projects.Participants interested in neuroimaging from any discipline are welcome. Ideal participants span in range from graduate students to professors across any disciplines willing to contribute (e.g., mathematics, computer
science, engineering, neuroscience, psychology, psychiatry, neurology, medicine, art, etc…). The primary requirement is a desire to work in close collaborations with people outside of your specialization in order to
address neuroscience questions that are beyond the expertise of a single discipline.One should come to brainhack ready to engage into collaborative projects, and with some material (slides, ideas, data, tools) ready to start a project or a discussion panel. Brainhack will build on the successful techniques used in other unconferences to keep the meeting focused and productive. It is possible to start a project and build a team as early as today. Please have a look at the website for information on the conference and a sample of projects (from Brainhack 2012).
The Preliminary Schedule for Brainhack 2013 is available here.
***NEW*** We will be accepting and publishing Brainhack 2013 abstracts. Abstracts should be submitted when you register.
Registration is now open here
Girl who feels no pain could inspire new painkillers
A girl who does not feel physical pain has helped researchers identify a gene mutation that disrupts pain perception. The discovery may spur the development of new painkillers that will block pain signals in the same way.
People with congenital analgesia cannot feel physical pain and often injure themselves as a result – they might badly scald their skin, for example, through being unaware that they are touching something hot.
By comparing the gene sequence of a girl with the disorder against those of her parents, who do not, Ingo Kurth at Jena University Hospital in Germany and his colleagues identified a mutation in a gene called SCN11A.
This gene controls the development of channels on pain-sensing neurons. Sodium ions travel through these channels, creating electrical nerve impulses that are sent to the brain, which registers pain.
Blocked signals
Overactivity in the mutated version of SCN11A prevents the build-up of the charge that the neurons need to transmit an electrical impulse, numbing the body to pain. “The outcome is blocked transmission of pain signals,” says Kurth.
To confirm their findings, the team inserted a mutated version of SCN11A into mice and tested their ability to perceive pain. They found that 11 per cent of the mice with the modified gene developed injuries similar to those seen in people with congenital analgesia, such as bone fractures and skin wounds. They also tested a control group of mice with the normal SCN11A gene, none of which developed such injuries.
The altered mice also took 2.5 times longer on average than the control group to react to the “tail flick” pain test, which measures how long it takes for mice to flick their tails when exposed to a hot light beam. “What became clear from our experiments is that although there are similarities between mice and men with the mutation, the degree of pain insensitivity is more prominent in humans,” says Kurth.
The team has now begun the search for drugs that block the SCN11A channel. “It would require drugs that selectively block this but not other sodium channels, which is far from simple,” says Kurth.
Completely unexpected
"This is a cracking paper, and great science," says Geoffrey Woods of the University of Cambridge, whose team discovered in 2006 that mutations in another, closely related ion channel gene can cause insensitivity to pain. "It’s completely unexpected and not what people had been looking for," he says.
Woods says that there are three ion channels, called SCN9A, 10A and 11A, on pain-sensing neurons. People experience no pain when either of the first two don’t work, and agonising pain when they’re overactive. “With this new gene, it’s the opposite: when it’s overactive, they feel no pain. So maybe it’s some kind of gatekeeper that stops neurons from firing too often, but cancels pain signals completely when it’s overactive,” he says. “If you could get a drug that made SCN11A overactive, it should be a fantastic analgesic.”
"It’s fascinating that SCN11A appears to work the other way, and that could really advance our knowledge of the role of sodium channels in pain perception, which is a very hot topic,” says Jeffrey Mogil at McGill University in Canada, who was not involved in the new study.
(Source: newscientist.com)
New study finds link between neurons’ inability to repair DNA and neurodegeneration.
Amyotrophic lateral sclerosis (ALS) — also known as Lou Gehrig’s disease — is a neurodegenerative disease that destroys the neurons that control muscle movement. There is no cure for ALS, which kills most patients within three to five years of the onset of symptoms, and about 5,600 new cases are diagnosed in the United States each year.
MIT neuroscientists have found new evidence that suggests that a failure to repair damaged DNA could underlie not only ALS, but also other neurodegenerative disorders such as Alzheimer’s disease. These findings imply that drugs that bolster neurons’ DNA-repair capacity could help ALS patients, says Li-Huei Tsai, director of MIT’s Picower Institute for Learning and Memory and senior author of a paper describing the ALS findings in the Sept. 15 issue of Nature Neuroscience.
Neurons are some of the longest-living cells in the human body. While other cells are frequently replaced, our neurons are generally retained throughout our lifetimes. Consequently, neurons can accrue a lot of DNA damage and are especially vulnerable to its effects.
“Our genome is constantly under attack and DNA strand breaks are produced all the time. Fortunately, they are not a worry because we have the machinery to repair it right away. But if this repair machinery were to somehow become compromised, then it could be very devastating for neurons,” Tsai says.
Lead authors of the paper are Picower Institute postdoc Wen-Yuan Wang and research scientist Ling Pan.
Impaired repair
Tsai’s group has been interested in understanding the importance of DNA repair in neurodegenerative processes for several years. In a study published in 2008, they reported that DNA double-strand breaks precede neuronal loss in a mouse model that undergoes Alzheimer’s disease-like neurodegeneration and identified a protein, HDAC1, which prevents neuronal loss under these conditions.
HDAC1 is a histone deacetylase, an enzyme that regulates genes by modifying chromatin, which consists of DNA wrapped around a core of proteins called histones. HDAC1 activity normally causes DNA to wrap more tightly around histones, preventing gene expression. However, it turns out that cells, including neurons, also exploit HDAC1’s ability to tighten up chromatin to stabilize broken DNA ends and promote their repair.
In a paper published earlier this year in Nature Neuroscience, Tsai’s team reported that HDAC1 works cooperatively with another deacetylase called SIRT1 to repair DNA and prevent the accumulation of damage that could promote neurodegeneration.
When a neuron suffers double-strand breaks, SIRT1 migrates within seconds to the damaged sites, where it soon recruits HDAC1 and other repair factors. SIRT1 also stimulates the enzymatic activity of HDAC1, which allows the broken DNA ends to be resealed.
SIRT1 itself has recently gained notoriety as the protein that promotes longevity and protects against diseases including diabetes and Alzheimer’s disease, and Tsai’s group believes that its role in DNA repair contributes significantly to the protective effects of SIRT1.
In an attempt to further unveil other partners that work with HDAC1 to repair DNA, Tsai and colleagues stumbled upon a protein called Fused In Sarcoma (FUS). This finding was intriguing, Tsai says, because the FUS gene is one of the most common sites of mutations that cause inherited forms of ALS.
The MIT team found that FUS appears at the scene of DNA damage very rapidly, suggesting that FUS is orchestrating the repair response. One of its roles is to recruit HDAC1 to the DNA damage site. Without it, HDAC1 does not appear and the necessary repair does not occur. Tsai believes that FUS may also be involved in sensing when DNA damage has occurred.
Linking mutation and disease
At least 50 mutations in the FUS gene have been found to cause ALS. The majority of these mutations occur in two sections of the FUS protein. The MIT team mapped the interactions between FUS and HDAC1 and found that these same two sections of the FUS protein bind to HDAC1.
They also generated four FUS mutants that are most commonly seen in ALS patients. When they replaced the normal FUS with these mutants, they found that the interaction with HDAC1 was impaired and DNA damage was significantly increased. This suggests that those mutations prevent FUS from recruiting HDAC1 when DNA damage occurs, allowing damage to accumulate and eventually leading to ALS.
The researchers also analyzed brain tissue samples from ALS patients harboring FUS mutations and found that the amount of DNA damage in neurons in motor cortex was about double that found in normal brain tissue.
ALS patients with FUS mutations usually develop the disease early, before age 40. Only one of a person’s two copies of the FUS gene needs to be mutated to produce the disease. Tsai says that early in life, having one copy of the normal FUS gene may be enough to keep DNA repair going. “With aging, eventually the machinery is compromised and it contributes to neuronal demise,” she says.
The findings suggest that drugs that promote DNA damage repair, including activators of HDAC1 and SIRT1, could help combat the effects of ALS. SIRT1 activators are now being developed and have entered clinical trials to treat diabetes.
“There are numerous human inherited DNA-repair deficiency syndromes, many of which show neurodegeneration or other neurological defects. This new study now extends the spectrum of neuropathology caused by defects in DNA maintenance to include ALS,” says Peter McKinnon, a professor of genetics at St. Jude Children’s Research Hospital who was not part of the research team. “This study offers new avenues to explore in the quest for treatment strategies.”
Tsai’s lab is now studying whether there is a direct relationship between FUS and SIRT1. She also wants to determine whether the DNA damage that occurs in ALS patients after FUS is lost occurs in certain “hotspots” or is random. “I would speculate that there’s got to be hotspots in terms of where the DNA is damaged. But right now it remains speculation,” she says. “We really need to do the experiments and demonstrate whether that’s the case.”
Electro-shock therapy sees a resurgence
The procedure is widely accepted by the medical community, although it lingers in the public imagination as a crude medical holdover.
The patients are rolled on gurneys into a small screened-off area at Park Royal Hospital every 15 minutes with assembly line regularity.
One is a woman in her 60s, who, like the others, gets a momentary jolt of electricity sent through her head, causing a brain seizure and her body to tense for several seconds. The hope: That this treatment — the electroconvulsive, or “electro-shock,” therapy — will ease the symptoms of her bipolar disorder that has so far not responded well to drugs.
The procedure, one of thousands performed at Park Royal since the 76-bed hospital opened last year, has worked on the woman in the past, says Dr. Ivan Mazzorana, who performs all of them on patients here. And, he said, it’s likely to do so again.
These days, the treatment goes by its more clinical-sounding acronym, “ECT.”
"When you bring it up, most people say, ‘Oh my God! Not ECT, that’s something from the past,’" Mazzorana said. "It’s a very simple procedure, safer, and it’s a lot quicker than the medication."
Electroconvulsive therapy today is a procedure widely accepted by the medical community and one, absent a rare court order, that is done with patient consent. But it is also a treatment that lingers in the public imagination as a crude medical holdover almost as dated as bloodletting. Many outside of psychiatry are surprised to learn that the procedure still exists at all.
Despite that, ECT has seen a resurgence at many health centers in recent decades, experts say.
Park Royal, the only inpatient psychiatric hospital in Lee County, Fla., has already treated nearly 200 people with ECT, most receiving multiple treatments. The number represents roughly 10 percent of all of Park Royal’s admissions since it opened in early 2012.
The hospital is a for-profit facility owned by the Tennessee-based Acadia Healthcare Co.
Most of those who have received ECT at Park Royal — patient ages have ranged from 18 years to those in their 90s — suffer from severe depression or bi-polar disorders. About 90 percent are inpatients. Others are referred from other parts of Florida, according to the hospital. A few are snowbirds who come in for ETC “maintenance” treatments.
The Mayo Clinic calls the treatment, which has a reported success rate of 70 percent to 80 percent, the “gold standard” treatment for severe depression. The most common side effect, according to proponents, is temporary short-term memory loss.
"I was afraid, to be honest with you," said Ron Spesia, a 71-year-old Fort Myers Beach retiree who suffered a deep, multiyear depression that did not respond to medication. He had 12 treatments and said he started feeling better after the third. "Then one day I decided, ‘Hey, you know what? It’s time to put the big boy pants on and pursue this.’ Smartest move I ever made."
Still, ECT has its critics. Some, including patients of decades past and anti-ECT groups, say it is little more than intentional brain damage. This, despite the psychiatric community’s endorsement of it and positive testimonials from many of the estimated 100,000 Americans who get the treatment each year.
A Fort Myers News-Press reporter was recently allowed to witness about a half dozen such procedures at Park Royal.
But even hospital administrators remain sensitive to the ECT stigma. Though a patient agreed to be photographed during one such procedure, and to have it recorded on video, the hospital overruled that consent.
The hospital also prohibited patient interviews inside the building, though other medical facilities routinely allow such interactions if patients are willing. David Edson, Park Royal’s director of business development, cited concerns about privacy and “the very delicate nature of the ECT treatment.”
Despite that, Mazzorana said he wants to demystify the treatment and those who get it.
"It seems like an extreme, dramatic treatment," Mazzorana said. "It’s a matter of really educating the psychiatric community, so then we can educate patients."
Mundane process
The treatments at Park Royal begin at 7 a.m. Mondays, Wednesdays and Fridays, and continue throughout the mornings. Staff usually see up to 10 ECT patients on these days.
The process bears little resemblance to its horrific depictions in popular culture. At Park Royal, it starts when patients come to a medical preparation area adjacent to the ECT treatment room, where staff hook them up to IVs — they will eventually get medication to paralyze their muscles during the treatment — as well as heart and brain monitors attached to their skin.
After a quick chat with medical staff, who assess their conditions, patients bite down on foam “bite blocks” before they are put fully under.
Flashlight-shaped paddles coated with a blue conductive gel are placed on each temple (bilateral treatment) or one goes on the right temple and one on the top of the head (unilateral treatment), depending on the type of ECT the patients need. Bilateral ECT is recommended in more severe cases of mental illness and may produce more memory loss, experts say.
Following a quick buzzing sound, patients’ bodies tense for about five seconds. Patients typically wake a minute or so after the procedure and are sent off to a recovery area until the anesthesia fully wears off. They remember nothing of the treatment itself.
New patients must typically stay in the hospital for the first half of the standard dozen ECT treatments.
Spesia, the former ECT patient, said the IV injection was the most painful part of the process. The most unpleasant, he said was the hospital stay. Now, months after the process, he said the only lingering side effect has been some short-term memory loss.
"All I can remember is them giving me the rubber bite block and then them putting the (anesthesia) mask on and telling me to breathe deeply." he said. "Absolutely painless."
Nancy Kish, a 74-year-old Fort Myers resident who has received dozens of treatments over the years, said her memory of treatments from years past is fuzzy but her mind is otherwise as sharp as it has ever been. She said the treatment is a better alternative to the high doses of medication she otherwise took, drugs that largely left her bed-ridden.
"I feel pretty good," said Kish. "I get upset easy, and I get anxiety attacks. But other than that, I’m better than what I was."
Much like the therapeutic mystery behind anti-depressant medication experts are not exactly sure why ECT works for some patients.
Mazzorana said two theories dominate: One says that electroconvulsive therapy enhances certain beneficial brain chemicals that are lacking in different parts of the brain. Another states that it causes the release of hormones that have a beneficial effect on mood and promote the growth of healthy brain cells, he said. Other recent research suggests that ECT works by reducing “hyper-connectivity” in the minds of severely depressed patients.
Endorsements
Whatever the exact mechanism, ECT’s endorsements include the American Psychiatric Association, the American Medical Association, and the U.S. Surgeon General.
"When you raise ECT, people’s eyes always roll up in their heads and their family says, ‘Oh my God, you’re a monster!’" said Fort Myers psychiatrist Steve Machlin, who performed the procedure more than a decade ago. "There’s always going to be people on the outside who say it’s not proven but, if you’ve looked at the science, it’s been proven to be effective."
Another Southwest Florida psychiatrist and researcher, Fred Schaerf, said opposition to the treatment is largely anti-psychiatry bias and from the treatment’s early days, when it was performed without anesthesia.
"I think there is a misconception about the treatment — that it’s barbaric, cruel," Schaerf said. "It has to do with that stigma and people’s belief system with psychiatry."
Most insurance, including Medicare, covers the treatment.
Edson, the Park Royal Hospital business development director, said the health center generally charge insurers $500 a treatment, though that does not include the costs of the anesthesiologist and hospital stay. Mazzorana said the total cost is about $1,000.
Opposition
Medical and patient endorsements aside, some patient groups believe it does little more than cause brain damage. A quick Internet search turns up a long list of anti-ECT websites, many of which include testimonials from people claiming to have suffered negative effects from the treatments.
Among the most vocal opponents is the Philadelphia-based National Mental Health Consumers’ Self Help Clearinghouse, which urged the U.S. Food and Drug Administration in 2011 not to reduce federal oversight of ECT devices. It also sharply criticized the Surgeon General’s endorsement of ECT in 1999.
The group points to published studies suggesting that ECT leads to memory loss and may be far more dangerous for the elderly than medication alone. Susan Rogers, the organization’s director, said patients aren’t warned enough about the risks.
"People are not given the opportunity for truly informed consent," said Rogers, who has not had the procedure herself. "People are not advised of the enormous risks as well as the benefits. They’re given a whitewashed version of the facts. They’re not told it might cause permanent cognitive impairment, and I think that’s wrong."
She said she is not opposed to the treatment itself.
"Apparently about 100,000 people a year receive ECT in the United States and, I’m sure for many of those people, they’re satisfied with those results," she said. "There are also many people who feel that ECT has destroyed their lives."
The psychiatric community commonly uses the one in 10,000 patients mortality figure (or one per 80,000 treatments), figures anti-ECT groups say dramatically under-estimate the risk, particularly among older patients. A 1995 USA TODAY investigation found that it may have been as high as one in 200 among elderly patients, based on some state reports at the time and some earlier studies.
A recent Department of Veterans Affairs review of ECT between 1999 and 2010 found no ECT deaths at VA hospitals during that period. It placed the mortality risk at one per 14,000 patients, or one per 73,400 treatments.
Florida does not closely track ECT usage. But Texas, which does, reported that none of the 2,079 patients receiving ECT last year died during the procedure. Two died shortly after treatment in 2012, the state report noted, but neither case was related to the treatment.
Five years of reports show that roughly 2 percent of patients experience some level of memory loss shortly after treatment.
None of Park Royal’s ECT patients have died during the procedure, said Christina Brownwood, the hospital’s ECT coordinator. Nor have any needed emergency medical care immediately after a treatment, she said.
Genes for body symmetry may also control handedness
Lefties and righties can thank same DNA that puts hearts on left side for hand dominance
Left- or right-handedness may be determined by the genes that position people’s internal organs.
About 10 percent of people prefer using their left hand. That ratio is found in every population in the world and scientists have long suspected that genetics controls hand preference. But finding the genes has been no simple task, says Chris McManus, a neuropsychologist at University College London who studies handedness but was not involved in the new research.
“There’s no single gene for the direction of handedness. That’s clear,” McManus says. Dozens of genes are probably involved, he says, which means that one person’s left-handedness might be caused by a variant in one gene, while another lefty might carry variants in an entirely different gene.
To find handedness genes, William Brandler, a geneticist at the University of Oxford, and colleagues conducted a statistical sweep of DNA from 3,394 people. Statistical searches such as this are known as genome-wide association studies; scientists often do such studies to uncover genes that contribute to complex diseases or traits such as diabetes and height. The people in this study had taken tests involving moving pegs on a board. The difference in the amount of time they took with one hand versus the other reflected how strongly left- or right-handed they were.
A variant in a gene called PCSK6 was most tightly linked with strong hand preference, the researchers report in the Sept. 12 PLOS Genetics. The gene has been implicated in handedness before, including in a 2011 study by the same research group. PCSK6 is involved in the asymmetrical positioning of internal organs in organisms from snails to vertebrates.
Brandler, who happens to be a lefty, knew the gene wasn’t the only cause of hand preference, so he and his colleagues looked at other genetic variants that didn’t quite cross the threshold of statistical significance. Many of the genes the team uncovered had previously been shown in studies of mice to be necessary for correctly placing organs such as the heart and liver. Four of the genes when disrupted in mice can cause cilia-related diseases. Cilia are hairlike appendages on cells that act a bit like GPS units and direct many aspects of development of a wide range of species, including humans.
One of the cilia genes, GLI3, also helps build the corpus callosum, a bundle of nerves that connects the two hemispheres of the brain. Some studies have suggested that the structure is bigger in left-handers.
It’s still a mystery how these genes direct handedness, says Larissa Arning, a human geneticist at Ruhr University Bochum in Germany. In addition to genes that direct body plans, she says, the study suggests that many more yet-to-be-discovered genes probably play a role in handedness.
Brandler hopes the study will also help remove some of the stigma of being left-handed. Left-handedness isn’t a character flaw or a sign of being sinister, he says: “It’s an outcome of genetic variation.”
(Source: sciencenews.org)
Think twice, speak once: Bilinguals process both languages
Bilingual speakers can switch languages seamlessly, likely developing a higher level of mental flexibility than monolinguals, according to Penn State linguistic researchers.
"In the past, bilinguals were looked down upon," said Judith F. Kroll, Distinguished Professor of Psychology, Linguistics and Women’s Studies. "Not only is bilingualism not bad for you, it may be really good. When you’re switching languages all the time it strengthens your mental muscle and your executive function becomes enhanced."
Fluent bilinguals seem to have both languages active at all times, whether both languages are consciously being used or not, the researchers report in a recent issue of Frontiers in Psychology. Both languages are active whether either was used only seconds earlier or several days earlier.
Bilinguals rarely say a word in the unintended language, which suggests that they have the ability to control the parallel activity of both languages and ultimately select the intended language without needing to consciously think about it.
The researchers conducted two separate but related experiments. In the first, 27 Spanish-English bilinguals read 512 sentences, written in either Spanish or English — alternating language every two sentences. Participants read the sentences silently until they came across a word displayed in red, at which point they were instructed to read the red word out loud, as quickly and accurately as possible. About half of the red words were cognates — words that look and sound similar and have the same meaning in both languages.
"Cognate words were processed more quickly than control words," said Jason W. Gullifer, a graduate student in psychology, suggesting that both languages are active at the same time.
Participants in the second experiment performed the same tasks as those in the first experiment, but this time were presented one language at a time. The second experiment’s results were similar to the first, suggesting that context does not influence word recognition.
"The context of the experiment didn’t seem to matter," said Gullifer. "If you look at bilinguals there seems to be some kind of mechanistic control."
Low Omega-3 could explain why some children struggle with reading
An Oxford University study has shown that a representative sample of UK schoolchildren aged seven to nine years had low levels of key Omega-3 fatty acids in their blood. Furthermore, the study found that children’s blood levels of the long-chain Omega-3 DHA (the form found in most abundance in the brain) ‘significantly predicted’ how well they were able to concentrate and learn. Oxford University researchers explained the findings, recently published in the journal PLOS ONE, at a conference in London on 4 September.
The study was presented at the conference by co-authors Dr Alex Richardson and Professor Paul Montgomery from Oxford University’s Centre for Evidence-Based Intervention in the Department of Social Policy and Intervention. It is one of the first to evaluate blood Omega-3 levels in UK schoolchildren. The long-chain Omega-3 fats (EPA and DHA) found in fish, seafood and some algae, are essential for the brain’s structure and function as well as for maintaining a healthy heart and immune system. Parents also reported on their child’s diet, revealing to the researchers that almost nine out of ten children in the sample ate fish less than twice a week, and nearly one in ten never ate fish at all. The government’s guidelines for a healthy diet recommend at least two portions of fish a week. This is because like vitamins, omega-3 fats have to come from our diets – and although humans can in theory make some EPA and DHA from shorter-chain omega-3 (found in some vegetable oils), research has shown this conversion is not reliable, particularly for DHA, say the researchers.
Blood samples were taken from 493 schoolchildren, aged between seven and nine years, from 74 mainstream schools in Oxfordshire. All of the children were thought to have below-average reading skills, based on national assessments at the age of seven or their teachers’ current judgements. Analyses of their blood samples showed that, on average, just under two per cent of the children’s total blood fatty acids were Omega-3 DHA (Docosahexaenoic acid) and 0.5 per cent were Omega-3 EPA (Eicosapentaenoic acid), with a total of 2.45 per cent for these long-chain Omega-3 combined. This is below the minimum of 4 per cent recommended by leading scientists to maintain cardiovascular health in adults, with 8-12 per cent regarded as optimal for a healthy heart, the researchers reported.
Co-author Professor Paul Montgomery said: ‘From a sample of nearly 500 schoolchildren, we found that levels of Omega-3 fatty acids in the blood significantly predicted a child’s behaviour and ability to learn. Higher levels of Omega-3 in the blood, and DHA in particular, were associated with better reading and memory, as well as with fewer behaviour problems as rated by parents and teachers. These results are particularly noteworthy given that we had a restricted range of scores, especially with respect to blood DHA but also for reading ability, as around two-thirds of these children were still reading below their age-level when we assessed them. Although further research is needed, we think it is likely that these findings could be applied generally to schoolchildren throughout the UK.’
Co-author Dr Alex Richardson added: ‘The longer term health implications of such low blood Omega-3 levels in children obviously can’t be known. But this study suggests that many, if not most UK children, probably aren’t getting enough of the long-chain Omega-3 we all need for a healthy brain, heart and immune system. That gives serious cause for concern because we found that lower blood DHA was linked with poorer behaviour and learning in these children.
‘Most of the children we studied had blood levels of long-chain Omega-3 that in adults would indicate a high risk of heart disease. This was consistent with their parents’ reports that most of them failed to meet current dietary guidelines for fish and seafood intake. Similarly, few took supplements or foods fortified with these Omega-3.’
The current findings build on earlier work by the same researchers, showing that dietary supplementation with Omega-3 DHA improved both reading progress and behaviour in children from the general school population who were behind on their reading. Their previous research has already shown benefits of supplementation with long-chain omega-3 (EPA+DHA) for children with ADHD, Dyspraxia, Dyslexia, and related conditions. The DHA Oxford Learning and Behaviour (DOLAB) Studies have now extended these findings to children from the general school population.
‘Technical advances in recent years have enabled the measurement of individual Omega-3 and other fatty acids from fingerstick blood samples. ‘These new techniques have been revolutionary – because in the past, blood samples from a vein were needed for assessing fatty acids, and that has seriously restricted research into the blood Omega-3 status of healthy UK children until now,’ said Dr Richardson.
(Source: ox.ac.uk)
Researchers Pinpoint Molecular Path that Makes Antidepressants Act Quicker in Mouse Model
Understanding alternate pathways for how mental meds work could lead to faster-acting drug targets
The reasons behind why it often takes people several weeks to feel the effect of newly prescribed antidepressants remains somewhat of a mystery – and likely, a frustration to both patients and physicians.
(Image: Mouse hippocampus expressing the Cre- virus. Credit: Julie Blendy, PhD; Brigitta Gunderson, PhD; Perelman School of Medicine, University of Pennsylvania)
Julie Blendy, PhD, professor of Pharmacology, at the Perelman School of Medicine, University of Pennsylvania; Brigitta Gunderson, PhD, a former postdoctoral fellow in the Blendy lab, and colleagues, have been working to find out why and if there is anything that can be done to shorten the time in which antidepressants kick in.
“Our goal is to find ways for antidepressants to work faster,” says Blendy.
The proteins CREB and CREM are both transcription factors, which bind to specific DNA sequences to control the “reading” of genetic information from DNA to messenger RNA (mRNA). Both CREB and CREM bind to the same 8-base-pair DNA sequence in the cell nucleus. But, the comparative influence of CREM versus CREB on the action of antidepressants is a “big unknown,” says Blendy.
CREB, and CREM to some degree, has been implicated in the pathophysiology of depression, as well as in the efficacy of antidepressants. However, whenever CREB is deleted, CREM is upregulated, further complicating the story.
Therefore, how an antidepressant works on the biochemistry and behavior in a mouse in which the CREB protein is deleted only in the hippocampus versus a wild type mouse in which CREM is overexpressed let the researchers tease out the relative influence of CREB and CREM on the pharmacology of an antidepressant. They saw the same results in each type of mouse line – increased nerve-cell generation in the hippocampus and a quicker response to the antidepressant. Their findings appear in the Journal of Neuroscience.
“This is the first demonstration of CREM within the brain playing a role in behavior, and specifically in behavioral outcomes, following antidepressant treatment,” says Blendy.
A Flood of Neurotransmitters
Antidepressants like SSRIs, NRIs, and older tricyclic drugs work by causing an immediate flood of neurotransmitters like serotonin, norepinephrine, and in some cases dopamine, into the synaptic space. However, it can take three to four weeks for patients to feel changes in mental state. Long-term behavioral effects of the drugs may take longer to manifest themselves, because of the need to activate CREB downstream targets such as BDNF and trkB, or as of yet unidentified targets, which could also be developed as new antidepressant drug targets.
The Penn team compared the behavior of the control, wild-type mice to the CREB mutant mice using a test in which the mouse is trained to eat a treat – Reese’s Pieces, to be exact – in the comfort of their home cage. The treat-loving mice are then placed in a new cage to make them anxious. They are given the treat again, and the time it takes for the mouse to approach the treat is recorded.
Animals that receive no drug treatment take a long time to venture out into the anxious environment to retrieve the treat, however, if given an antidepressant drug for at least three weeks, the time it takes a mouse to get the treat decreases significantly, from about 400 seconds to 100 seconds. In mice in which CREB is deleted or in mice in which CREM is upregulated, this reduction happens in one to two days versus the three weeks seen in wild-type mice.
The accelerated time to approach the treat in mice on the medication was accompanied by an increase in new nerve growth in the hippocampus.
“Our results suggest that activation of CREM may provide a means to accelerate the therapeutic efficacy of current antidepressant treatment,” says Blendy. Upregulation of CREM observed after CREB deletion, appears to functionally compensate for CREB loss at a behavioral level and leads to maintained or increased expression of some CREB target genes. The researchers’ next step is to identify any unique CREM target genes in brain areas such as the hippocampus, which may lead to the development of faster-acting antidepressants.
(Source: uphs.upenn.edu)
Insulin plays a role in mediating worms’ perceptions and behaviors
Using salt-sniffing roundworms, Salk scientists help explain how the nervous system processes sensory information
In the past few years, as imaging tools and techniques have improved, scientists have been working tirelessly to build a detailed map of neural connections in the human brain—with the ultimate hope of understanding how the mind works.
But determining how cells in the brain are physically connected is only the first clue for decoding our perceptions and behaviors. We also need to know the precise routes that information takes in the brain in a given context. Now, publishing their results September 8, 2013, in the journal Nature Neuroscience, researchers at the Salk Institute for Biological Studies have shown a striking example of the flexibility in neural circuitry and its influence on behaviors in worms, depending on the animals’ environment.
The roundworm Caenorhabditis elegans has exactly 302 neurons—far less than the estimated 100 billion neurons a person has—and we already know how each of them is connected. That, in addition to how easily the tiny creature’s cells can be manipulated, allows researchers to ask what sort of information passes through the circuits—in molecular-and circuit-level detail—and what are the behavioral consequences of this information flow.
Even with a comprehensive map of the worm’s neuronal connections in hand, however, scientists still don’t know how the animal can interact with its environment in thousands of different ways. That’s one big question that Sreekanth Chalasani, an assistant professor in Salk’s Molecular Neurobiology Laboratory and Sarah Leinwand, a doctoral student at the University of California, San Diego, sought to answer.
In C. elegans, thanks to studies performed more than 20 years ago, many sensory neurons were identified to have distinct roles such as sensing temperature, pheromones, salt and odors. To know what these cells did, scientists had zapped them one-by-one with a laser and measured the worms’ behaviors. These studies implicated one neuron in the detection of increased salt in the worm’s surroundings.
In the new study, rather than ablating individual sensory neurons, Leinwand and Chalasani imaged worms that expressed genetically encoded calcium indicators in their neurons, which caused the cells to light up when active. Surprisingly, after exposure to an attractive but high concentration of salt, the worms’ olfactory sensory neuron lit up.
"We were extremely surprised to see that with these new tools, these new calcium sensors, we could discover that there was more than one type of neuron involved in processing sensory cues that people had thought were only sensed by single neurons," says Leinwand.
Using additional genetic manipulations and behavioral assays, the researchers showed that the olfactory neuron—while still important for sensing odorants—was crucial for the worm’s movement toward salt within a certain concentration range. Unexpectedly, this neuron’s response to salt also required the previously identified salt-sensing neuron. In fact, the olfactory neuron was not directly sensing salt but instead was being activated by the salt sensory neuron, they found.
What information was the salt-sensing neuron sending to the olfactory neuron? Neurons communicate with each other by sending chemical and electrical signals through close contacts with their neighbors. By testing worms whose signaling molecules had been genetically knocked out, Chalasani and Leinwand could see which were playing a role in transmission when the worm was stimulated by higher salt. From these experiments, they saw that a neuropeptide, a small protein present in neurons, was being released by the salt-sensing neuron to shape the animal’s behavior.
Identifying the neuropeptide (or neuropeptides) responsible for the context-dependent signaling was the most challenging part of the study, because the worm has 115 genes that code for some 250 neuropeptides, Chalasani says. Luckily, there are only four different molecular machines that process all of these peptides; by using genetic knockouts of each of the four, Leinwand and Chalasani were quickly able to narrow the list down to about 40 genes which coded for insulin neuropeptides.
One by one, the team tracked olfactory neuron responses to high salt in worms missing each gene, finding that worms lacking the gene for an insulin neuropeptide known as INS-6 did not respond to increases in salt. Putting this peptide back restored the animal’s normal responses to high salt.
"It was rewarding to see that, while there might be more than one peptide signal, the contributions from INS-6 are certainly significant," Leinwand says. She and Chalasani also found the specific receptor on the receiving end of the olfactory neurons.
That insulin was the main signaling molecule recruiting the olfactory neuron into a salt-sensing circuit was a big surprise.
"Traditionally, neuropeptides have been thought to modulate neuronal function over many seconds to many minutes," Chalasani says. "But in this particular instance, it looks like the insulin is acting in less than a second to transfer information from the salt-sensing neuron to the neuron which normally responds to odor."
Similar neuropeptide communication may also create flexible neural circuits that mediate the diverse behaviors that other animals and people perform in their environments. Insulin has many roles in people—it has been implicated in aging and metabolism, for example—but so far it has only been shown to function on a slower, minute time-scale.
Chalasani and Leinwand plan to investigate whether there are other fast neural circuit switches in worms—and if so, whether those switches act through neuropeptide signaling or some other mechanism. They’re also interested in how the circuit switch changes as the animal ages. “You would expect that as the animal is aging, some of this communication becomes less efficient,” Chalasani says.
Modifying the activity of neuronal networks that encode spatial memories leads to the formation of an incorrect fear memory in mice
The formation and retrieval of memories allows all kinds of organisms, including humans, to learn and thrive in their environment. Yet our memories are not always accurate, and mistaken remembrances can have important consequences, such as in the justice system and in our navigation of the world. Susumu Tonegawa, Steve Ramirez, Xu Liu and colleagues at the RIKEN-MIT Center for Neural Circuit Genetics, have gained insight into the creation of mistaken memories by using light activation of neurons to generate an incorrect fear memory in mice.
The researchers allowed mice to explore a novel location and used genetic techniques to label neurons in the hippocampus—a part of the brain linked to spatial memory—that were activated in the process with a special channel called channelrhodopsin-2. The cells that expressed this channel could then be artificially activated by light. In this way, the researchers were able to reactivate neurons that fired in that particular location, even if the mice were no longer there.
They then moved the mice to another location where they were exposed to foot shocks, causing the mice to exhibit immobility, a fear behavior. At the same time, the researchers used light to activate the channelrhodopsin-2-expressing neurons that had fired in the first location.
When Tonegawa and his colleagues moved the animals to a third location, they did not show fear behavior. Yet when the mice went back to the first location, where they had never experienced a foot shock, the mice now exhibited prominent freezing behavior. The researchers had generated a ‘false memory’ in the mice of foot shocks in a location in which they had never been exposed to them.
The researchers showed that light reactivation of neuronal networks in the central area of the hippocampus, called the dentate gyrus, could create false memories, while reactivation of the outer ‘CA1’ area of the hippocampus could not. Tonegawa and his colleagues suggest that this is because mouse exploration of different locations leads to activation of more overlapping neuronal networks in the CA1 than in the dentate gyrus. “This may reflect the fundamental differences of how memories are encoded in these two regions,” explains Liu.
The findings provide insight into how the brain encodes and processes memories and could one day lead to treatments for post-traumatic stress disorder. “Our work may also have implications for situations where patients mix reality with their own imaginations, such as in schizophrenia,” says Liu.