Posts tagged science
Articles and news from the latest research reports.
Altering eye cells may one day restore vision
Doctors may one day treat some forms of blindness by altering the genetic program of the light-sensing cells of the eye, according to scientists at Washington University School of Medicine in St. Louis.
Working in mice with retinitis pigmentosa, a disease that causes gradual blindness, the researchers reprogrammed the cells in the eye that enable night vision. The change made the cells more similar to other cells that provide sight during daylight hours and prevented degeneration of the retina, the light-sensing structure in the back of the eye. The scientists now are conducting additional tests to confirm that the mice can still see.
“We think it may be significantly easier to preserve vision by modifying existing cells in the eye than it would be to introduce new stem cells,” says senior author Joseph Corbo, MD, PhD, assistant professor of pathology and immunology. “A diseased retina is not a hospitable environment for transplanting stem cells.”
The study is available in the early online edition of Proceedings of the National Academy of Sciences.
Mutations in more than 200 genes have been linked to various forms of blindness. Efforts are underway to develop gene therapies for some of these conditions.
Rather than seek treatments tailored to individual mutations, Corbo hopes to develop therapies that can alleviate many forms of visual impairment. To make that possible, he studies the genetic factors that allow cells in the developing eye to take on the specialized roles necessary for vision.
In the 19th century, a speechless patient wasted away in the Bicetre Hospital in France for 21 years. He was known as ‘Tan’ for the only word he could say, and for 150 years, his identity has remained a mystery. In 1861, as Tan lay dying, the famous physician Paul Broca encountered the patient. When the ill-fated patient died, Broca autopsied his brain. Broca noticed a lesion in a part of the brain tucked up behind the eyes. He concluded that the brain region was responsible for language processing. But despite Tan becoming one of the most famous medical patients in history, he was never identified until now.
A 2007 study in the journal Brain revealed the extent of the lesion using MRI imaging. A recent study identified the patient as a Monsieur Louis Leborgne, a craftsman who had suffered from epilepsy his whole life.
Tests conducted on Israel’s Ariel Sharon reveal significant brain activity
A team of American and Israeli brain scientists tested former Israeli Prime Minister Ariel Sharon to assess his brain responses, using functional magnetic resonance imaging (fMRI). Surprisingly, Sharon showed significant brain activity.
The team consisted of Martin Monti, an assistant professor of psychology and neurosurgery at UCLA, professors Alon Friedman, Galia Avidan and Tzvi Ganel of the Zlotowski Center for Neuroscience at Israel’s Ben-Gurion University of the Negev, and Dr. Ilan Shelef, head of medical imaging at Israel’s Soroka University Medical Center.
The 84-year-old Sharon, presumed to be in a vegetative state since suffering a brain hemorrhage in 2006, was scanned last week to assess the extent and quality of his brain processing, using methods recently developed by Monti and his colleagues. The test lasted approximately two hours.
The scientists showed Sharon pictures of his family, had him listen to his son’s voice and used tactile stimulation to assess the extent to which his brain responded to external stimuli.
To their surprise, significant brain activity was observed in each test, in specific brain regions, indicating appropriate processing of these stimulations, Monti said.
The scientists conducted three tests to assess Sharon’s level of consciousness. They asked him to imagine he was hitting a tennis ball and to imagine he was walking through the rooms of his home. They also showed him a photograph of a face superimposed on a photo of a house, asking him to focus first on the face and then on the house. The scientists found encouraging, but subtle, signs of consciousness.
"Information from the external world is being transferred to the appropriate parts of Mr. Sharon’s brain. However, the evidence does not as clearly indicate whether Mr. Sharon is consciously perceiving this information," Monti said. "We found faint brain activity indicating that he was complying with the tasks. He may be minimally conscious, but the results were weak and should be interpreted with caution."
Tzvi Ganel, who initiated the project, stressed that Sharon’s family wished to employ these new techniques not only for the benefit of the former prime minister but also for other families in a similar situation.
Protein Family Linked to Autism Suppresses the Development of Inhibitory Synapses
Synapse development is promoted by a variety of cell adhesion molecules that connect neurons and organize synaptic proteins. Many of these adhesion molecules are linked to neurodevelopmental disorders; mutations in neuroligin and neurexin proteins, for example, are associated with autism and schizophrenia. According to a study in The Journal of Cell Biology, another family of proteins linked to these disorders regulates the function of neuroligins and neurexins in order to suppress the development of inhibitory synapses.
Like neurexins and neuroligins, the neuronal proteins MDGA1 and MDGA2 have been linked to autism and schizophrenia, but their function in neurodevelopment was unknown. Both MDGA proteins localize to the plasma membrane, and their extracellular domains are similar to those of cell adhesion molecules. On the other hand, postsynaptic neuroligin proteins are known to help synapses form by associating with neurexins on presynaptic membranes. Neuroligin-2 specifically boosts the development of inhibitory synapses, whereas neuroligin-1 promotes the development of excitatory synapses.
Ann Marie Craig and colleagues from the University of British Columbia investigated the function of MDGAs using co-culture assays, in which postsynaptic proteins like neuroligin-1 or -2 are expressed in non-neuronal cells and then tested for their ability to induce presynaptic differentiation in neighboring neurons. MDGA1 didn’t promote synapse formation in these assays. Instead, it inhibited the ability of neuroligin-2 to promote synapse development. The researchers found that MDGA1’s extracellular domains bound to neuroligin-2, blocking its association with neurexin. The same domains were sufficient to inhibit neuroligin-2’s synapse-promoting activity. In contrast, MDGA1 didn’t show high affinity binding to, or inhibit the function of, neuroligin-1. This suggested that, by inhibiting neuroligin-2, MDGA1 might specifically suppress the development of inhibitory synapses, so Craig and colleagues investigated MDGA1 function in cultured hippocampal neurons.
“Overexpressing MDGA1 in neurons reduced the density of inhibitory synapses without affecting excitatory synapses,” Craig says. Knocking down MDGA1, on the other hand, increased inhibitory synapse development but had no effect on excitatory synapses.
“I can’t think of any other proteins that specifically suppress inhibitory synapse formation,” says Craig. Indeed, very few proteins in general have been identified as negative regulators of synapse development, compared to the many proteins that are known to promote synaptogenesis. The results suggest that function-altering mutations in the MDGA proteins may disrupt the balance of excitatory and inhibitory synapses in the brain, potentially explaining the development of autism and other neurodevelopmental disorders.
“This puts MDGAs in the same pathway as neurexins and neuroligins and strengthens the evidence for the involvement of synaptic organizing proteins in autism and schizophrenia,” Craig explains. As well as investigating the function of MDGA2, the researchers want to explore the therapeutic potential of MDGA1 inhibitors, not only against autism and schizophrenia but also for the treatment of epilepsy, in which excitatory and inhibitory synapses are also imbalanced.
(Source)
Cardiac Disease Linked to Higher Risk of Mental Impairment
Cardiac disease is associated with increased risk of mild cognitive impairment such as problems with language, thinking and judgment — particularly among women with heart disease, a Mayo Clinic study shows. Known as nonamnestic because it doesn’t include memory loss, this type of mild cognitive impairment may be a precursor to vascular and other non-Alzheimer’s dementias, according to the findings published online Monday in JAMA Neurology.
Mild cognitive impairment is an important stage for early detection and intervention in dementia, says lead author, Rosebud Roberts, M.B., Ch.B., a health sciences researcher at Mayo Clinic.
"Prevention and management of cardiac disease and vascular risk factors are likely to reduce the risk," Roberts says.
Researchers evaluated 2,719 people ages 70 to 89 at the beginning of the study and every 15 months after. Of the 1,450 without mild cognitive impairment at the beginning, 669 had heart disease and 59 (8.8 percent) developed nonamenestic mild cognitive impairment; in comparison 34 (4.4 percent) of 781 who did not have heart disease developed nonamenestic mild cognitive impairment.
The association varied by sex; cardiac disease and mild cognitive impairment appeared together more often among women than in men.
(Source)
New research uncovers the neural mechanism underlying drug cravings
Addiction may result from abnormal brain circuitry in the frontal cortex, the part of the brain that controls decision-making. Researchers from the RIKEN Center for Molecular Imaging Science in Japan collaborating with colleagues from the Montreal Neurological Institute of McGill University in Canada report today that the lateral and orbital regions of the frontal cortex interact during the response to a drug-related cue and that aberrant interaction between the two frontal regions may underlie addiction. Their results are published today in the journal Proceedings of the National Academy of Sciences of the USA.
Cues such as the sight of drugs can induce cravings and lead to drug-seeking behaviors and drug use. But cravings are also influenced by other factors, such as drug availability and self-control. To investigate the neural mechanisms involved in cue-induced cravings the researchers studied the brain activity of a group of 10 smokers, following exposure to cigarette cues under two different conditions of cigarette availability. In one experiment cigarettes were available immediately and in the other they were not. The researchers combined a technique called transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI).
The results demonstrate that in smokers the orbitofrontal cortex (OFC) tracks the level of craving while the dorsolateral prefrontal cortex (DPFC) is responsible for integrating drug cues and drug availability. Moreover, the DPFC has the ability to suppress activity in the OFC when the cigarette is unavailable. When the DPFC was inactivated using TMS, both craving and craving-related signals in the OFC became independent of drug availability.
The authors of the study conclude that the DLPFC incorporates drug cues and knowledge on drug availability to modulate the value signals it transmits to the OFC, where this information is transformed into drug-seeking action.
"We demonstrate that in smokers, cravings build up in the OFC upon processing of cigarette cues and availability by the DFPC. What is surprising is that this is a neural circuit involved in decision making and self-control, that normally guides individuals to optimal behaviors in daily life." Explains Dr. Hayashi, from RIKEN, who designed and conducted the fMRI and TMS experiments.
"This research uncovers the brain circuitry responsible for self-control during reward-seeking choices. It is also consistent with the view that drug addiction is a pathology of decision making." According to Dr. Alain Dagher, a neurologist at the Montreal Neurological Institute.
These findings will help understand the neural basis of addiction and may contribute to a therapeutic approach for addiction.
(Image: New Jersey Addiction Assistance)
When food porn holds no allure: the science behind satiety
New research from the University of British Columbia is shedding light on why enticing pictures of food affect us less when we’re full.
“We’ve known that insulin plays a role in telling us we’re satiated after eating, but the mechanism by which this happens is unclear,” says Stephanie Borgland, an assistant professor in UBC’s Dept. of Anesthesiology, Pharmacology and Therapeutics and the study’s senior author.
In the new study published online this week in Nature Neuroscience, Borgland and colleagues found that insulin – prompted by a sweetened, high-fat meal – affects the ventral tegmental area (VTA) of the brain, which is responsible for reward-seeking behaviour. When insulin was applied to the VTA in mice, they no longer gravitated towards environments where food had been offered.
“Insulin dulls the synapses in this region of the brain and decreases our interest in seeking out food,” says Borgland, “which in turn causes us to pay less attention to food-related cues.”
“There has been a lot of discussion around the environmental factors of the obesity epidemic,” Borgland adds, pointing to fast food advertising bans in Quebec, Norway, the U.K., Greece and Sweden. “This study helps explain why pictures or other cues of food affect us less when we’re satiated – and may help inform strategies to reduce environmental triggers of overeating.”
The VTA has also been shown to be associated with addictive behaviours, including illicit drug use. Borgland says better understanding of the mechanism in this region of the brain could, in the long run, inform diagnosis and treatment.
(Image: Shutterstock)
Glial cells assist in the repair of injured nerves
Unlike the brain and spinal cord, the peripheral nervous system has an astonishing capacity for regeneration following injury. Researchers at the Max Planck Institute of Experimental Medicine in Göttingen have discovered that, following nerve damage, peripheral glial cells produce the growth factor neuregulin1, which makes an important contribution to the regeneration of damaged nerves.
From their cell bodies to their terminals in muscle or skin, neuronal extensions or axons in the peripheral nervous system are surrounded along their entire length by glial cells. These cells, which are known as Schwann cells, envelop the axons with an insulating sheath called myelin, which enables the rapid transmission of electrical impulses. Following injury to a peripheral nerve, the damaged axons degenerate. After a few weeks, however, they regenerate and are then recovered with myelin by the Schwann cells. For thus far unexplained reasons, however, the Schwann cells do not manage to regenerate the myelin sheaths completely. Thus the function of damaged nerves often remains permanently impaired and certain muscles remain paralysed in affected patients.
In a current research study, the scientists have succeeded in showing that the growth factor neuregulin1 supports nerve repair and the redevelopment of the myelin layer. This protein is usually produced by neurons and is localised on axons where it acts as an important signal for the maturation of Schwann cells and myelin formation. Because the axons rapidly degenerate after injury, the remaining Schwann cells lose their contact with the axons. They thus lack the neuregulin1 signal of the nervous fibres. “In the phase following nerve damage, in which the axons are missing, the Schwann cells must carry out many tasks without the help of axonal signals. If the Schwann cells cannot overcome this first major obstacle in the aftermath of nerve injury, the nerve cannot be adequately repaired,” explains Ruth Stassart, one of the study authors.
To prevent this, the Schwann cells themselves take over the production of the actual neuronal signal molecule. After nerve damage, they synthesise the neuregulin1 protein until the axons have grown again. With the help of genetically modified mice, the researchers working on this study were able to show that the neuregulin1 produced in Schwann cells is necessary for the new maturation of the Schwann cells and the regeneration of the myelin sheath after injury. “In mice that lack the neuregulin1 gene in their Schwann cells, the already incomplete nerve regeneration process is extensively impaired,” explains co-author Robert Fledrich.
The researchers would now like to examine in greater detail how the Schwann cells contribute to the complete repair of myelinated axons after nerve damage, so that this information can also be used for therapeutic purposes.
Neuroscientists pinpoint location of fear memory in amygdala
A rustle of undergrowth in the outback: it’s a sound that might make an animal or person stop sharply and be still, in the anticipation of a predator. That “freezing” is part of the fear response, a reaction to a stimulus in the environment and part of the brain’s determination of whether to be afraid of it.
A neuroscience group at Cold Spring Harbor Laboratory (CSHL) led by Assistant Professor Bo Li Ph.D., together with collaborator Professor Z. Josh Huang Ph.D., today release the results of a new study that examines the how fear responses are learned, controlled, and memorized. They show that a particular class of neurons in a subdivision of the amygdala plays an active role in these processes.
Locating fear memory in the amygdala
Previous research had indicated that structures inside the amygdalae, a pair of almond-shaped formations that sit deep within the brain and are known to be involved in emotion and reward-based behavior, may be part of the circuit that controls fear learning and memory. In particular, a region called the central amygdala, or CeA, was thought to be a passive relay for the signals relayed within this circuit.
Li’s lab became interested when they observed that neurons in a region of the central amygdala called the lateral subdivision, or CeL, “lit up” in a particular strain of mice while studying this circuit.
“Neuroscientists believed that changes in the strength of the connections onto neurons in the central amygdala must occur for fear memory to be encoded,” Li says, “but nobody had been able to actually show this.”
This led the team to further probe into the role of these neurons in fear responses and furthermore to ask the question: If the central amygdala stores fear memory, how is that memory trace read out and translated into fear responses?
To examine the behavior of mice undergoing a fear test the team first trained them to respond in a Pavlovian manner to an auditory cue. The mice began to “freeze,” a very common fear response, whenever they heard one of the sounds they had been trained to fear.
To study the particular neurons involved, and to understand them in relation to the fear-inducing auditory cue, the CSHL team used a variety of methods. One of these involved delivering a gene that encodes for a light-sensitive protein into the particular neurons Li’s group wanted to look at.
By implanting a very thin fiber-optic cable directly into the area containing the photosensitive neurons, the team was able to shine colored laser light with pinpoint accuracy onto the cells, and in this manner activate them. This is a technique known as optogenetics. Any changes in the behavior of the mice in response to the laser were then monitored.
A subset of neurons in the central amygdala controls fear expression
The ability to probe genetically defined groups of neurons was vital because there are two sets of neurons important in fear-learning and memory processes. The difference between them, the team learned, was in their release of message-carrying neurotransmitters into the spaces called synapses between neurons. In one subset of neurons, neurotransmitter release was enhanced; in another it was diminished. If measurements had been taken across the total cell population in the central amygdala, neurotransmitter levels from these two distinct sets of neurons would have been averaged out, and thus would not have been detected.
Li’s group found that fear conditioning induced experience-dependent changes in the release of neurotransmitters in excitatory synapses that connect with inhibitory neurons – neurons that suppress the activity of other neurons – in the central amygdala. These changes in the strength of neuronal connections are known as synaptic plasticity.
Particularly important in this process, the team discovered, were somatostatin-positive (SOM+) neurons. Somatostatin is a hormone that affects neurotransmitter release. Li and colleagues found that fear-memory formation was impaired when they prevent the activation of SOM+ neurons.
SOM+ neurons are necessary for recall of fear memories, the team also found. Indeed, the activity of these neurons alone proved sufficient to drive fear responses. Thus, instead of being a passive relay for the signals driving fear learning and responses in mice, the team’s work demonstrates that the central amygdala is an active component, and is driven by input from the lateral amygdala, to which it is connected.
“We find that the fear memory in the central amygdala can modify the circuit in a way that translates into action — or what we call the fear response,” explains Li.
In the future Li’s group will try to obtain a better understanding of how these processes may be altered in post-traumatic stress disorder (PTSD) and other disorders involving abnormal fear learning. One important goal is to develop pharmacological interventions for such disorders.
Li says more research is needed, but is hopeful that with the discovery of specific cellular markers and techniques such as optogenetics, a breakthrough can be made.
Mediterranean diet may not protect brain
Hopes that a Mediterranean diet would be as good for the head as it is for the heart may have been dampened by a French study that found little benefit for aging brains from the diet rich in fruit, vegetables, whole grains, nuts, wine and olive oil.
The study, published in the American Journal of Clinical Nutrition, looked at the participants’ dietary patterns in middle age and measured their cognitive performance at around age 65, but found no connection between Mediterranean eating and mental performance.
"Our study does not support the hypothesis of a significant neuroprotective effect of a (Mediterranean diet) on cognitive function," writes study leader Emmanuelle Kesse-Guyot at the nutritional epidemiology research centre of the French national health research agency INSERM.
It’s been suggested that the “good” fats in the Mediterranean diet might benefit the brain directly, or that low saturated fats and high fiber in the diet could help stave off cognitive decline indirectly by keeping blood vessels healthy.
Previous research has seemed to uphold that premise.
One large study in the US Midwest, for example, found that people in their 60s and older who ate a mostly Mediterranean diet were less prone to mental decline as they aged. Another study of residents of Manhattan linked a Mediterranean-style diet to a 40 per cent lower risk of Alzheimer’s disease.
No significant difference
Researchers in the French study used data on 3083 people who were followed from the mid-1990s, when they were at least 45 years old.
At the beginning of the study, participants recorded what they ate over one 24-hour period every two months, for a total of six dietary record samples per year. Then, between 2007 and 2009 when the participants were about 65 years old, their memory and other mental abilities were measured.
Researchers then separated participants into three categories depending on how closely they adhered to a Mediterranean-style diet, and compared their mental ability test scores.
Overall, they found that people who ate a diet closest to the Mediterranean ideal performed about the same as those who ate a non-restricted diet.
Associate Professor Nikos Scarmeas, of New York’s Columbia University Medical Center, was not involved with the study but has researched the effects of food on brain health. He says it’s important to note that the new study had some limitations.
For instance, researchers only tested the participants’ mental abilities once, making it impossible to track whether they got better or worse over time, adds Scarmeas.
"We don’t have the strong evidence to go and tell people, ‘Listen, if you follow this diet, it will improve cognition’," he says.
(Image: mediterraneandiet.com)