Posts tagged science
Articles and news from the latest research reports.
Melatonin delays ALS symptom onset and death in mice
Melatonin injections delayed symptom onset and reduced mortality in a mouse model of the neurodegenerative condition amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, according to a new study by researchers at the University of Pittsburgh School of Medicine. In a report published online ahead of print in the journal Neurobiology of Disease, the team revealed that receptors for melatonin are found in the nerve cells, a finding that could launch novel therapeutic approaches.
Annually about 5,000 people are diagnosed with ALS, which is characterized by progressive muscle weakness and eventual death due to the failure of respiratory muscles, said senior investigator Robert Friedlander, M.D., UPMC Endowed Professor of neurosurgery and neurobiology and chair, Department of Neurological Surgery, Pitt School of Medicine. But the causes of the condition are not well understood, thwarting development of a cure or even effective treatments.
Melatonin is a naturally occurring hormone that is best known for its role in sleep regulation. After screening more than a thousand FDA-approved drugs several years ago, the research team determined that melatonin is a powerful antioxidant that blocks the release of enzymes that activate apoptosis, or programmed cell death.
"Our experiments show for the first time that a lack of melatonin and melatonin receptor 1, or MT1, is associated with the progression of ALS," Dr. Friedlander said. "We saw similar results in a Huntington’s disease model in an earlier project, suggesting similar biochemical pathways are disrupted in these challenging neurologic diseases."
Hoping to stop neuron death in ALS just as they did in Huntington’s, the research team treated mice bred to have an ALS-like disease with injections of melatonin or with a placebo. Compared to untreated animals, the melatonin group developed symptoms later, survived longer, and had less degeneration of motor neurons in the spinal cord.
"Much more work has to be done to unravel these mechanisms before human trials of melatonin or a drug akin to it can be conducted to determine its usefulness as an ALS treatment," Dr. Friedlander said. "I suspect that a combination of agents that act on these pathways will be needed to make headway with this devastating disease."
(Source: eurekalert.org)
Scientists identify important regulator for synapse stability and plasticity
Using the fruit fly as a model organism, neurobiologists from the Friedrich Miescher Institute for Biomedical Research have identified the L1-type CAM neuroglian as an important regulator for synapse growth, function and stability. They show that the interaction of neuroglian with ankyrin provides a regulatory module to locally control synaptic connectivity and function.
A Drosophila neuromuscular junction. Motoneuron membrane (blue), synaptic vesicles (green), postsynaptic density (red)
From its earliest beginnings until an organism’s death, the nervous system changes. Connections between nerve cells are formed, stabilized and disassembled not only during the development of the brain in the womb and in early childhood, but also in adults as they learn or form memories. In this flow of change, cell adhesion molecules (CAMs), which mediate cell-cell interactions, are thought to provide stability and guidance in a Velcro-like-manner as synapses change.
Jan Pielage and his group at the Friedrich Miescher Institute for Biomedical Research have carried out an unbiased genetic screen to identify cell adhesion molecules that control synapse maintenance and plasticity, using the fruit fly, Drosophila. As they publish in the latest issue of PLOS Biology, they identified the cell adhesion molecule called neuroglian as a key regulator for synapse stability.
Neuroglian is a transmembrane protein with a large extracellular domain and an intracellular signaling domain. Through the extracellular domain interactions with CAMs on neighboring cells are established. This stabilizes the site and is a prerequisite for synapse formation. “We think that the extracellular interactions of neuroglian are essential for neurite outgrowth and axon targeting during early development,” explains Pielage.
The scientists could then show that the intracellular domain, which interacts with the adaptor molecule called ankyrin, modulates the stability of synapses. At the neuromuscular junction, where nerve cells innervate the muscle, the strength of the interaction of neuroglian with ankyrin modulates the balance between synapse growth and stability. As the binding affinity of ankyrin for neuroglian decreased, e.g. due to phosphorylation, the mobility of neuroglian within the motorneuron increased. This change in mobility caused the destabilization of synapses but at the same time, it allowed the formation of new synapses at other places. “This organization permits easy regulation, and allows the fine tuning of synaptic connectivity along one nerve cell without disrupting the neuronal network or impairing overall circuit stability,” said Pielage.
In the central nervous system, where synapses are formed between two neurons, a homophilic interaction of neuroglian is required to establish the contact between pre- and postsynaptic neurons. A differential regulation of ankyrin binding is then necessary to coordinate transsynaptic development and to enable synapse maturation and function. “Modulation of the neuroglian-ankyrin interaction might enable local and precise control of synaptic connectivity,” comments Pielage.
This comprehensive structure function study provides a molecular basis for previous observations linking mutations in the ankyrin binding domain of the human homologue of neuroglian, L1CAM, to neurological L1/CRASH disorders that include mental retardation.
(Source: fmi.ch)
Suppressing Protein May Stem Alzheimer’s Disease Process
Scientists funded by the National Institutes of Health have discovered a potential strategy for developing treatments to stem the disease process in Alzheimer’s disease. It’s based on unclogging removal of toxic debris that accumulates in patients’ brains, by blocking activity of a little-known regulator protein called CD33.
“Too much CD33 activity appears to promote late-onset Alzheimer’s by preventing support cells from clearing out toxic plaques, key risk factors for the disease,” explained Rudolph Tanzi, Ph.D., of Massachusetts General Hospital and Harvard University, a grantee of the NIH’s National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). “Future medications that impede CD33 activity in the brain might help prevent or treat the disorder.”
Tanzi and colleagues report on their findings April 25, 2013 in the journal Neuron.
“These results reveal a previously unknown, potentially powerful mechanism for protecting neurons from damaging toxicity and inflammation,” said NIMH Director Thomas R. Insel, M.D. “Given increasing evidence of overlap between brain disorders at the molecular level, understanding such workings in Alzheimer’s disease may also provide insights into other mental disorders.”
Variation in the CD33 gene turned up as one of four prime suspects in the largest genome-wide dragnet of Alzheimer’s-affected families, reported by Tanzi and colleagues in 2008. The gene was known to make a protein that regulates the immune system, but its function in the brain remained elusive. To discover how it might contribute to Alzheimer’s, the researchers brought to bear human genetics, biochemistry and human brain tissue, mouse and cell-based experiments.
They found over-expression of CD33 in support cells, called microglia, in postmortem brains from patients who had late-onset Alzheimer’s disease, the most common form of the illness. The more CD33 protein on the cell surface of microglia, the more beta-amyloid protein and plaques – damaging debris – had accumulated in their brains. Moreover, the researchers discovered that brains of people who inherited a version of the CD33 gene that protected them from Alzheimer’s conspicuously showed reduced amounts of CD33 on the surface of microglia and less beta-amyloid.
Brain levels of beta-amyloid and plaques were also markedly reduced in mice engineered to under-express or lack CD33. Microglia cells in these animals were more efficient at clearing out the debris, which the researchers traced to levels of CD33 on the cell surface.
Evidence also suggested that CD33 works in league with another Alzheimer’s risk gene in microglia to regulate inflammation in the brain.
The study results – and those of a recent rat study that replicated many features of the human illness – add support to the prevailing theory that accumulation of beta-amyloid plaques are hallmarks of Alzheimer’s pathology. They come at a time of ferment in the field, spurred by other recent contradictory evidence suggesting that these presumed culprits might instead play a protective role.
Since increased CD33 activity in microglia impaired beta-amyloid clearance in late onset Alzheimer’s, Tanzi and colleagues are now searching for agents that can cross the blood-brain barrier and block it.
(Source: nimh.nih.gov)
Study Shows How Parkinson’s Disease Protein Acts like a Virus
A protein known to be a key player in the development of Parkinson’s disease is able to enter and harm cells in the same way that viruses do, according to a Loyola University Chicago Stritch School of Medicine study.
The protein is called alpha-synuclein. The study shows how, once inside a neuron, alpha synuclein breaks out of lysosomes, the digestive compartments of the cell. This is similar to how a cold virus enters a cell during infection. The finding eventually could lead to the development of new therapies to delay the onset of Parkinson’s disease or halt or slow its progression, researchers said.
The study by virologist Edward Campbell, PhD, and colleagues, was published April 25, 2013 in the journal PLOS ONE.
Alpha-synuclein plays a role in the normal functioning of healthy neurons. But in Parkinson’s disease patients, the protein turns bad, aggregating into clumps that lead to the death of neurons in the area of the brain responsible for motor control. Previous studies have shown that these protein aggregates can enter and harm cells. Campbell and colleagues showed how alpha synuclein can bust out of lysosomes, small structures that collectively serve as the cell’s digestive system. The rupture of these bubble-like structures, known as vesicles, releases enzymes that are toxic to the rest of the cell.
“The release of lysosomal enzymes is sensed as a ‘danger signal’ by cells, since similar ruptures are often induced by invading bacteria or viruses,” said Chris Wiethoff, a collaborator on the study. “Lysosomes are often described as ‘suicide bags’ because when they are ruptured by viruses or bacteria, they induce oxidative stress that often leads to the death of the affected cell.”
In a viral or bacterial infection, the deaths of such infected cells may overall be a good thing for the infected individual. But in Parkinson’s disease, this same protective mechanism may lead to the death of neurons and enhance the spread of alpha-synuclein between cells in the brain, Campbell said. “This might explain the progressive nature of Parkinson’s disease. More affected cells leads to the spread of more toxic alpha-synuclein aggregates in the brain,” Campbell said. “This is very similar to what happens in a spreading viral infection.”
Campbell stressed that these studies need to be followed up and confirmed in other models of Parkinson’s disease. “Using cultured cells, we have made some exciting observations. However, we need to understand how lysosomal rupture is affecting disease progression in animal models of Parkinson’s disease and, ultimately, the brains of people affected by Parkinson’s disease. Can we interfere with the ability of alpha-synuclein to rupture lysosomes in these settings? And will that have a positive effect on disease progression? These are the questions we are excited to be asking next.”
Jeffrey H. Kordower, PhD, professor of neurological sciences, professor of neurosurgery and director of the Research Center for Brain Repair at Rush University Medical Center, said the study “is an important finding by a group of investigators who are beginning to make their impact in the field of Parkinson’s disease. This paper adds to the growing concept that alpha-synuclein, a main culprit in the cause of Parkinson’s disease, can transfer from cell to cell. This paper elegantly puts a mechanism behind such a transfer. The findings will help shape the direction of Parkinson’s disease research for years to come.”
Missing link in Parkinson’s disease found
Researchers at Washington University School of Medicine in St. Louis have described a missing link in understanding how damage to the body’s cellular power plants leads to Parkinson’s disease and, perhaps surprisingly, to some forms of heart failure.
These cellular power plants are called mitochondria. They manufacture the energy the cell requires to perform its many duties. And while heart and brain tissue may seem entirely different in form and function, one vital characteristic they share is a massive need for fuel.
Working in mouse and fruit fly hearts, the researchers found that a protein known as mitofusin 2 (Mfn2) is the long-sought missing link in the chain of events that control mitochondrial quality.
The findings are reported April 26 in the journal Science.
The new discovery in heart cells provides some explanation for the long known epidemiologic link between Parkinson’s disease and heart failure.
“If you have Parkinson’s disease, you have a more than two-fold increased risk of developing heart failure and a 50 percent higher risk of dying from heart failure,” says senior author Gerald W. Dorn II, MD, the Philip and Sima K. Needleman Professor of Medicine. “This suggested they are somehow related, and now we have identified a fundamental mechanism that links the two.”
Heart muscle cells and neurons in the brain have huge numbers of mitochondria that must be tightly monitored. If bad mitochondria are allowed to build up, not only do they stop making fuel, they begin consuming it and produce molecules that damage the cell. This damage eventually can lead to Parkinson’s or heart failure, depending on the organ affected. Most of the time, quality-control systems in a healthy cell make sure damaged or dysfunctional mitochondria are identified and removed.
Over the past 15 years, scientists have described much of this quality-control system. Both the beginning and end of the chain of events are well understood. And since 2006, scientists have been working to identify the mysterious middle section of the chain – the part that allows the internal environment of sick mitochondria to communicate to the rest of the cell that it needs to be destroyed.
“This was a big question,” Dorn says. “Scientists would draw the middle part of the chain as a black box. How do these self-destruct signals inside the mitochondria communicate with proteins far away in the surrounding cell that orchestrate the actual destruction?”
“To my knowledge, no one has connected an Mfn2 mutation to Parkinson’s disease,” Dorn says. “And until recently, I don’t think anybody would have looked. This isn’t what Mfn2 is supposed to do.”
Mitofusin 2 is known for its role in fusing mitochondria together, so they might exchange mitochondrial DNA in a primitive form of sexual reproduction.
“Mitofusins look like little Velcro loops,” Dorn says. “They help fuse together the outer membranes of mitochondria. Mitofusins 1 and 2 do pretty much the same thing in terms of mitochondrial fusion. What we have done is describe an entirely new function for Mfn2.”
The mitochondrial quality-control system begins with what Dorn calls a “dead man’s switch.”
“If the mitochondria are alive, they have to do work to keep the switch depressed to prevent their own self-destruction,” Dorn says.
Specifically, mitochondria work to import a molecule called PINK. Then they work to destroy it. When mitochondria get sick, they can’t destroy PINK and its levels begin to rise. Then comes the missing link that Dorn and his colleague Yun Chen, PhD, senior scientist, identified. Once PINK levels get high enough, they make a chemical change to Mfn2, which sits on the surface of mitochondria. This chemical change is called phosphorylation. Phosphorylated Mfn2 on the surface of the mitochondria can then bind with a molecule called Parkin that floats around in the surrounding cell.
Once Parkin binds to Mfn2 on sick mitochondria, Parkin labels the mitochondria for destruction. The labels then attract special compartments in the cell that “eat” and destroy the sick mitochondria. As long as all links in the quality-control system work properly, the cells’ damaged power plants are removed, clearing the way for healthy ones.
“But if you have a mutation in PINK, you get Parkinson’s disease,” Dorn says. “And if you have a mutation in Parkin, you get Parkinson’s disease. About 10 percent of Parkinson’s disease is attributed to these or other mutations that have been identified.”
According to Dorn, the discovery of Mfn2’s relationship to PINK and Parkin opens the doors to a new genetic form of Parkinson’s disease. And it may help improve diagnosis for both Parkinson’s disease and heart failure.
“I think researchers will look closely at inherited Parkinson’s cases that are not explained by known mutations,” Dorn says. “They will look for loss of function mutations in Mfn2, and I think they are likely to find some.”
Similarly, as a cardiologist, Dorn and his colleagues already have detected mutations in Mfn2 that appear to explain certain familial forms of heart failure, the gradual deterioration of heart muscle that impairs blood flow to the body. He speculates that looking for mutations in PINK and Parkin might be worthwhile in heart failure as well.
“In this case, the heart has informed us about Parkinson’s disease, but we may have also described a Parkinson’s disease analogy in the heart,” he says. “This entire process of mitochondrial quality control is a relatively small field for heart specialists, but interest is growing.”
Thanks to Rare Alpine Bacteria, Researchers Identify One of Alcohol’s Key Gateways to the Brain
Thanks to a rare bacteria that grows only on rocks in the Swiss Alps, researchers at The University of Texas at Austin and the Pasteur Institute in France have been the first to identify how alcohol might affect key brain proteins.
It’s a major step on the road to eventually developing drugs that could disrupt the interaction between alcohol and the brain.
“Now that we’ve identified this key brain protein and understand its structure, it’s possible to imagine developing a drug that could block the binding site,” said Adron Harris, professor of biology and director of the Waggoner Center for Alcohol and Addiction at The University of Texas at Austin.
Harris and his former postdoctoral fellow Rebecca Howard, now an assistant professor at Skidmore College, are co-authors on the paper that was recently published in Nature Communications. It describes the structure of the brain protein, called a ligand-gated ion channel, that is a key enabler of many of the primary physiological and behavioral effects of alcohol.
Harris said that for some time there has been suggestive evidence that these ion channels are important binding sites for alcohol. Researchers couldn’t prove it, however, because they couldn’t crystallize the brain protein well enough, and therefore couldn’t use X-ray crystallography to determine the structure of the protein with and without alcohol present.
“For many of us in the alcohol field, this has been a Holy Grail, actually finding a binding site for alcohol on the brain proteins and showing it with X-ray crystallography,” said Harris. “But it hasn’t been possible because it is not possible to get a nice crystal.”
The breakthrough came when Marc Delarue and his colleagues at the Pasteur Institute sequenced the genome of cyanobacteria Gloeobacter violaceus. They noted a protein sequence on the bacteria that is remarkably similar to the sequence of a group of ligand-gated ion channels in the human brain. They were able to crystallize this protein. Harris saw the results and immediately got in touch.
“This is something you never would have found with any sort of logical approach,” he said. “You never would have guessed that this obscure bacterium would have something that looks like a brain protein in it. But the institute, because of Pasteur’s fascination with bacteria, has this huge collection of obscure bacteria, and over the last few years they’ve been sequencing the genomes, keeping an eye out for interesting properties.”
Harris and Howard asked their French colleagues to collaborate, got the cyanobacteria, changed one amino acid to make it sensitive to alcohol, and then crystallized both the original bacteria and the mutated one. They compared the two to see whether they could identify where the alcohol bound to the mutant. With further tests they confirmed that it was a meaningful site.
“Everything validated that the cavity in which the alcohol bound is important,” said Harris. “It doesn’t account for all the things that alcohol does, but it appears to be important for a lot of them, including some of the ‘rewarding’ effects and some of the negative, aversive effects.”
Going forward, Harris and his lab plan to use mice to observe how changes to the key protein affect behavior when the mice consume alcohol.
They’re also hoping to identify other important proteins from this family of ligand-gated ion channels. In the long term, he hopes to be involved in developing drugs that act on these proteins in ways that help people diminish or cease their drinking.
“So why do some people drink moderately and some excessively?” he said. “One reason lies in that the balance between the rewarding and the aversive effects, and that balance is different for different people, and it can change within an individual depending on their drinking patterns. Some of those effects are determined by the interactions of alcohol and these channels, so the hope is that we can alter the balance. Maybe we can diminish the reward or increase the aversive effects.”
New research findings on the brain’s guardian cells
Researcher Johan Jakobsson and his colleagues have now published their results in Nature Communications.
At present, researchers know very little about exactly how microglia work. At the same time, there is a lot of curiosity and high hopes among brain researchers that greater understanding of microglia could lead to entirely new drug development strategies for various brain diseases”, says Johan Jakobsson, research group leader at the Division of Molecular Neurogenetics at Lund University.
What the researchers have now succeeded in identifying is a deviation in the structure of the microglia cells, which makes it possible to visualise them and study their behaviour. By inserting a luminescent protein controlled by a microscopic molecule, microRNA-9, the researchers can now distinguish the microglia and monitor their function over time in the brains of rats and mice.
It has long been known that microglia form the first line of defence of the immune system in diseases of the brain. They move quickly to the affected area and release an arsenal of molecules that protect the nerve cells and clear away damaged tissue.
New research also suggests that microglia not only guard the nerve cells but also play an important role in their basic function.
“This represents a real step forward in technological development. Now we can view microglia in a way that has not been possible before. We and our colleagues now hope to be able to use this technique to study the role of the cells in different disease models, for example Parkinson’s disease and stroke, in which microglia are believed to play an important role”, explains Johan Jakobsson.
New hope for autistic children who never learn to speak
An Autistica consultation published this month found that 24% of children with autism were non-verbal or minimally verbal, and it is known that these problems can persist into adulthood. Professionals have long attempted to support the development of language in these children but with mixed outcomes. An estimated 600,000 people in the UK and 70 million worldwide have autism, a neuro-developmental condition which is life-long.
Today, scientists at the University of Birmingham publish a paper in Frontiers in Neuroscience showing that while not all of the current interventions used are effective, there is real hope for progress by using interventions based on understanding natural language development and the role of motor and “motor mirroring” behaviour in toddlers.
The researchers, led by Dr Joe McCleery, who is supported by autism research charity Autistica, examined over 200 published papers and more than 60 different intervention studies, and found that:
- Motor behaviours, such as banging toys and copying gestures or facial expressions (“mirroring”), play a key role in the learning of language.
- Children with autism show specific motor impairments, and less “mirroring” brain activity, particularly in relation to strangers in whom they show very little interest. This finding may hold the key to language problems overall.
- Despite extensive use of sign language training to improve speech and communication skills in non-verbal children with autism, there is very little evidence that it makes a positive impact, potentially due to the impairments in motor behaviours and mirroring.
- Picture exchange training can lead to improvements in speech. Here, children gradually learn to “ask” for things by exchanging pictures. This may work well because it does not depend on complex motor skills or mirroring.
- Play-based approaches which employ explicit teaching strategies and are developmentally based are particularly successful.
- New studies involving a focus on motor skills alongside speech and language intervention are showing promising preliminary results. This is exciting because these interventions utilise our new understanding of the role of motor behaviours in the development of speech and social interaction.
With the support of Autistica, the UK’s leading autism research charity, Dr McCleery’s team have now embarked on new work which builds on these findings to design interventions which specifically target the aspects of development where there are deficits in non-verbal autistic children.
Dr McCleery says: “We feel that the field is approaching a turning point, with potentially dramatic breakthroughs to come in both our understanding of communication difficulties in people with autism, and the potential ways we can intervene to make a real difference for those children who are having difficulties learning to speak.”
Christine Swabey, CEO of Autistica, says: “80% of the parents in our recent consultation wanted interventions straight after diagnosis. Dr McCleery’s work shows how critical it is for all intervention to be evidence-based, and that the best approaches are based on a real understanding of the development of difficulties in autism. We are proud to be supporting the next steps in this vital research which will improve the quality of life for people with autism.”
Alison Hardy, whose son Alfie is six, says: “As a parent of an autistic child, who is non-verbal, I feel quite vulnerable. People are always saying “try this, it worked wonders for us”. But you can’t try everything. We need a proper, scientific evidence base for what works and what does not. Then we can focus our time and our effort, with some confidence that we have a chance of helping our children. The publication of this research is an exciting step in giving us that confidence, it is great that Autistica is supporting this vital work.”
(Source: eurekalert.org)
Transgenic mice ready to fight obesity – and more
Scientists at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw investigate mice with a very precisely modified genome. Because it is possible to turn off the Dicer gene in adult mice, they can be used to investigate the processes related to such cognitive functions such as learning and memory. Also Nencki scientists have just shown that the new transgenic mouse is suitable to study metabolic dysfunctions resulting in obesity.
Studies on the Dicer gene and its impact on the cognitive and metabolic processes are currently carried out at the Nencki Institute’s Laboratory of Animal Models, a core facility in the newly established Neurobiology Center. The Center has been built on Campus Ochota in Warsaw as part of a large European project called the Centre for Preclinical Research and Technology (CePT). This project, financed from the Operational Programme Innovative Economy, brings together 10 research institutions from Warsaw.
“No one needs convincing that knowledge about the function of individual human genes is absolutely fundamental in biology as well as medicine”, says Dr Witold Konopka, head of the Laboratory of Animal Models. “But how do we determine a gene’s function, if no genetic modifications in humans are allowed? The only method is to create an animal, for example a mouse with genes turned on or off to model the studied illness. This is easy to say, but difficult to do, especially when the involved genes are really important for each cell”.
For several years Dr Konopka has been involved in research on the Dicer gene in mice. This gene, the analogue of which can be found also in the human genome, is responsible for creating a protein which reduces RNA molecules to short, 20-nucleotide fragments, important in regulating the activity of other genes. The Dicer gene needs to be active for proper functioning of the cell. It cannot be simply turned off in zygote, because the resulting defect would make the proper development of the zygote impossible.
Preparation of a transgenic mouse, in which the Dicer gene could be blocked in adulthood, takes a year and a half. This process starts with surrounding the Dicer gene on the DNA chain with two sequences known as loxP. This is done on stem cells, which are then injected into the embryo. Since the Dicer gene remains active, the embryo develops normally. At the same time the animal zygote of the opposite sex is injected with a gene coding a protein known as recombinase Cre-ERT2. Molecules of this protein consist of a part containing the Cre enzyme and a fragment reacting to a chemical compound called tamoxifen, which prior to such reaction prohibits recombinase Cre-ERT2 from penetrating into the cell nucleus.
Adult mice of both types are then cross bred for progeny, which will inherit the Dicer gene surrounded with the loxP sequences as well as the gene coding for recombinase from its parents. A mouse of this type has been created thanks to a joint effort of research groups from different world research centres such as the German Cancer Research Center (DKFZ) in Germany or the Imperial College London in the United Kingdom.
In order to turn off the Dicer gene in such adult mouse, it is enough to administer tamoxifen to them for a few days, which accumulates in neurons and allows the recombinase to penetrate into the cell nucleus. The Cre enzyme recognises the loxP sequence and removes the coding fragment with the Dicer gene.
“The first mice, in which the Dicer gene could be switched off at any time, were received by me a few years ago during my postdoctoral fellowship in the German Cancer Research Center in Heidelberg. Currently we breed such mice also the Nencki’s Laboratory of Animal Models. But breeding such animals constitutes only a part of the task. If we want to use them for research, they have to be appropriately characterized”, explains Dr Konopka.
Traits of mice used for scientific research have to be well known. Without such knowledge researchers cannot determine whether a change observed in the appearance or behaviour of the animal is related to turning off the gene. “Two years ago we have characterized the cognitive processes of these new mice. We have determined that after turning off the Dicer gene the animals showed better memory than the controls”, says Dr Konopka. But about five months after deleting the Dicer gene from the brain, the mice scored below the level of the control group on their cognitive abilities, which could be related to dying neurons devoid of the Dicer gene. Currently scientists have just finished analysing changes occurring in metabolic processes of those new mice, which for 3-4 weeks after turning off the Dicer gene eat more and gain weight faster, whereupon their appetite goes back to normal, but higher weight of their bodies’ remains.
“Before we have established with the required accuracy, how our mice learn and remember. Now we are certain, that the same mice can be used to investigate obesity and we plan to do that soon. But in our new lab we will not only conduct studies on disease models. We would also like to generate new transgenic animals for other research centres”, emphasizes Dr Konopka.
(Source: alphagalileo.org)
Clenching Right Fist May Give Better Grip On Memory
Clenching your right hand may help form a stronger memory of an event or action, and clenching your left may help you recollect the memory later, according to research published April 24 in the open access journal PLOS ONE by Ruth Propper and colleagues from Montclair State University.
Participants in the research study were split into groups and asked to first memorize, and later recall words from a list of 72 words. There were 4 groups who clenched their hands; One group clenched their right fist for about 90 seconds immediately prior to memorizing the list and then did the same immediately prior to recollecting the words. Another group clenched their left hand prior to both memorizing and recollecting. Two other groups clenched one hand prior to memorizing (either the left or right hand) and the opposite hand prior to recollecting. A control group did not clench their fists at any point.
The group that clenched their right fist when memorizing the list and then clenched the left when recollecting the words performed better than all the other hand clenching groups. This group also did better than the group that did not clench their fists at all, though this difference was not statistically ‘significant’.
"The findings suggest that some simple body movements — by temporarily changing the way the brain functions- can improve memory. Future research will examine whether hand clenching can also improve other forms of cognition, for example verbal or spatial abilities," says Ruth Propper, lead scientist on the study.
The authors clarify that further work is needed to test whether their results with word lists also extend to memories of visual stimuli like remembering a face, or spatial tasks, such as remembering where keys were placed. Based on previous work, the authors suggest that this effect of hand-clenching on memory may be because clenching a fist activates specific brain regions that are also associated with memory formation.