Neuroscience
Month
Drinking during pregnancy can have a severe, adverse effect on the central nervous systems of children after birth, researchers from Poland have discovered.
The study, which was presented Sunday at the annual meeting of the Radiological Society of North America (RSNA), looked at 200 children who were exposed to alcohol during their fetal stage, as well as 30 other kids whose mothers did not drink while pregnant or during lactation.
The researchers used a trio of different MRI techniques in order to study the brain development of both groups of subjects. First, they used standard MRI scans to observe the size and shape of the corpus callosum, which is a group of nerve fibers that oversees communication between the two halves of the brain.
Fetal alcohol exposure is believed to be one of the primary causes of impaired development of the corpus callosum, and sure enough, the MRI scans revealed those who had been exposed to alcohol had “statistically significant thinning of the corpus callosum… compared with the other group,” the RSNA said in a statement.
They also used diffusion weighted imaging (DWI) to study six areas of the central nervous system in both groups. The DWI technique maps the diffusion of water in the brain and can be more successful in detecting tissue abnormalities than regular MRI scans, the researchers explained.
Again, children who had been exposed to alcohol “exhibited statistically significant increases in diffusion on DWI” than their counterparts — an indication there had been damage to the brain tissue, or the presence of neurological disorders, according to Dr Andrzej Urbanik, chair of the Department of Radiology at Jagiellonian University.
Finally, they used proton (hydrogen) magnetic resonance spectroscopy (HMRS) to study the metabolism in the youngsters’ brains. The results uncovered “a high degree of metabolic changes that were specific for particular locations within the brain,” according to Dr. Urbanik.
The RSNA, citing US Centers for Disease Control and Prevention (CDC) statistics, reports as many as 1.5 out of every 1,000 children born alive suffer from fetal alcohol syndrome, and the costs of treating those victims tops $4 billion annually in America alone.
Researchers at Yale University have found that neural receptors in a fly’s antenna are able to communicate with one another despite a lack of synaptic connections. They suggest in their paper published in the journal Nature that the communication between the neurons occurs via electrical signals transported by shared fluids.
Suspecting that the fluid filled hairs in the antennas of the fly, Drosophila melanogaster, called sensilla, might possess a property known as ephaptic coupling, where nerve cells communicate without a direct link, the researchers tested the abilities of several fly specimens in their lab. The first focused on two receptors located in the sensilla responsible for detecting fruity methyl hexanoate and banana-scented 2-heptanone, respectively. When exposed to methyl hexonate, they found that only the first receptor fired. If heptanone were suddenly introduced however, the first receptor ceased firing immediately as the second commenced indicating that some form of communication between the two was occurring. They found that the reverse worked as well. To rule out possible modes of communication, the researchers conducted the same experiment with flies that had their synapses disabled via drugs and with others that had had their antennas physically cut off. Both showed the same results indicating that the communication was not direct but was localized.
In another experiment the researchers blocked a neuron in a sensilla responsible for detecting vinegar which was situated next to a neuron responsible for detecting carbon dioxide (for avoidance). When placed in a maze with two arms that smelled of carbon dioxide and one of vinegar, the fly headed for the vinegar scented arm, showing that the vinegar disabled neuron was still able to communicate with its carbon dioxide detecting partner.
The researchers suggest such an ability in flies might help in figuring out which path to take when encountering an environment filled with many different options. They also suggest that neuron pairs in the sensilla might be communicating with one another via electrical signals. When one detects what it’s supposed to detect, it sends a small charge into the fluid in which it and other neurons reside. That charge may then cause other neurons in the vicinity to go silent.
Researchers from McGill University and the University of Montreal have identified a crucial link between protein synthesis and autism spectrum disorders (ASD), which can bolster new therapeutic avenues. Regulation of protein synthesis, also termed mRNA translation, is the process by which cells manufacture proteins.
Autism spectrum disorders (ASD) encompass a wide array of neurodevelopmental diseases that affect three areas of behaviour: social interactions, communication and repetitive interests or behaviors. According to the U.S.-based Centers for Disease Control and Prevention, 1 in 88 children suffer from ASD, and the disorder is reported to occur in all racial, ethnic, and socioeconomic groups. ASDs are almost five times more common among boys (1 in 54) than among girls (1 in 252).
“My lab is dedicated to elucidating the role of dysregulated protein synthesis in cancer etiology. However, our team was surprised to discover that similar mechanisms may be implicated in the development of ASD”, explained Prof. Nahum Sonenberg, from McGill’s Dept. of Biochemistry, Faculty of Medicine, and the Goodman Cancer Research Centre. “We used a mouse model in which a key gene controlling initiation of protein synthesis was deleted. In these mice, production of neuroligins was increased. Neuroligins are important for the formation and regulation of connections known as synapses between neuronal cells in the brain and essential for the maintenance of the balance in the transmission of information from neuron to neuron.”
“Since the discovery of neuroligin mutations in individuals with ASD in 2003, the precise molecular mechanisms implicated remain unknown,” said Christos Gkogkas, a postdoctoral fellow at McGill and lead author. “Our work is the first to link translational control of neuroligins with altered synaptic function and autism-like behaviors in mice. The key is that we achieved reversal of ASD-like symptoms in adult mice. Firstly, we used compounds, which were previously developed for cancer treatment, to reduce protein synthesis. Secondly, we used non-replicating viruses as vehicles to put a break on exaggerated synthesis of neuroligins.”
Computer modeling played an important role in this research. “By using a new sophisticated computer algorithm that we specially developed to answer Dr. Sonenberg’s questions, we identified the unique structures of mRNAs of the neuroligins that could be responsible for their specific regulation,” explained Prof. François Major, of the University of Montreal’s Institute for Research in Immunology and Cancer and Department of Computer Science.
The researchers found that dysregulated synthesis of neuroligins augments synaptic activity, resulting in an imbalance between excitation and inhibition in single brain cells, opening up exciting new avenues for research that may unlock the secrets of autism.
“The autistic behaviours in mice were prevented by selectively reducing the synthesis of one type of neuroligin and reversing the changes in synaptic excitation in cells,” explained Prof. Jean-Claude Lacaille at the University of Montreal’s Groupe de Recherche sur le Système Nerveux Central and Department of Physiology. “In short, we manipulated mechanisms in brain cells and observed how they influence the behaviour of the animal.” The researchers were also able to reverse changes in inhibition and augment autistic behaviors by manipulating a second neuroligin. “The fact that the balance can be affected suggests that there could be a potential for pharmacological intervention by targeting these mechanisms,” Lacaille concluded.
MRI shows changes in the brains of people with post-concussion syndrome (PCS), according to a new study published online in the journal Radiology. Researchers hope the results point the way to improved detection and treatment for the disorder.
PCS affects approximately 20 percent to 30 percent of people who suffer mild traumatic brain injury (MTBI)—defined by the World Health Organization as a traumatic event causing brief loss of consciousness and/or transient memory dysfunction or disorientation. Symptoms of PCS include headache, poor concentration and memory difficulty.
Conventional neuroimaging cannot distinguish which MTBI patients will develop PCS.
"Conventional imaging with CT or MRI is pretty much normal in MTBI patients, even though some go on to develop symptoms, including severe cognitive problems," said Yulin Ge, M.D., associate professor, Department of Radiology at the NYU School of Medicine in New York City. "We want to try to better understand why and how these symptoms arise."
Dr. Ge’s study used MRI to look at the brain during its resting state, or the state when it is not engaged in a specific task, such as when the mind wanders or while daydreaming. The resting state is thought to involve connections among a number of regions, with the default mode network (DMN) playing a particularly important role.
"Baseline DMN is very important for information processing and maintenance," Dr. Ge said.
Alterations in DMN have been found in several psychiatric disorders, including Alzheimer’s disease, autism and schizophrenia, but little is known about DMN connectivity changes in MTBI.
For the new study, Dr. Ge and colleagues used resting-state functional MRI to compare 23 MTBI patients who had post-traumatic symptoms within two months of the injury and 18 age-matched healthy controls. Resting state MRI detects distinct changes in baseline oxygen level fluctuations associated with brain functional networks between patients with MTBI and control patients.
The MRI results showed that communication and information integration in the brain were disrupted among key DMN structures after mild head injury, and that the brain tapped into different neural resources to compensate for the impaired function.
"We found decreased functional connectivity in the posterior network of the brain and increased connectivity in the anterior component, probably due to functional compensation in patients with PCS," Dr. Ge said. "The reduced posterior connectivity correlated positively with neurocognitive dysfunction."
Dr. Ge and the other researchers hope to recruit additional MTBI patients for further studies with an eye toward developing a biomarker to monitor disease progression and recovery as well as treatment effects.
"We want to do studies to look at the changes in the network over time and correlate these functional changes with structural changes in the brain," he said. "This could give us hints on treatments to bring back cognitive function."
Scientists at the Mainz University Medical Center have discovered another molecule that plays an important role in regulating myelin formation in the central nervous system. Myelin promotes the conduction of nerve cell impulses by forming a sheath around their projections, the so-called axons, at specific locations – acting like the plastic insulation around a power cord. The research team, led by Dr. Robin White of the Institute of Physiology and Pathophysiology at the University Medical Center of Johannes Gutenberg University Mainz, recently published their findings in the prestigious journal EMBO reports.
Complex organisms have evolved a technique known as saltatory conduction of impulses to enable nerve cells to transmit information over large distances more efficiently. This is possible because the specialized nerve cell axonal projections involved in conducting impulses are coated at specific intervals with myelin, which acts as an insulating layer. In the central nervous system, myelin develops when oligodendrocytes, which are a type of brain cell, repeatedly wrap their cellular processes around the axons of nerve cells forming a compact stack of cell membranes, a so-called myelin sheath. A myelin sheath not only has a high lipid content but also contains two main proteins, the synthesis of which needs to be carefully regulated.
The current study analyzed the synthesis of myelin basic protein (MBP), a substance which is essential for the formation and stabilization of myelin membranes. In common with all proteins, MBP is generated in a two-stage process originating from basic genetic material in the form of DNA. First, DNA is converted to mRNA, which, in turn, serves as a template for the actual synthesis of MBP. During myelin formation, the synthesis of MBP in oligodendrocytes is suppressed until distinct signals from nerve cells initiate myelination at specific “production sites”. To date, the mechanisms involved in the suppression of MBP synthesis over relatively long periods of time have not been understood. This is where the current work of the Mainz scientists comes in, as they were able to identify a molecule that is responsible for the suppression of MBP synthesis.
"This molecule, called sncRNA715, binds to MBP mRNA, thus preventing MBP synthesis," explains Dr. Robin White. "Our research findings show that levels of sncRNA715 and MBP inversely correlate during myelin formation and that it is possible to influence the extent of MBP production in oligodendrocytes by artificially modifying levels of sncRNA715. This indicates that the recently discovered molecule is a significant factor in the regulation of MBP synthesis."
Understanding the molecular basis for myelin formation is essential with regard to various neurological illnesses that involve a loss of the protective myelin layer. For example, it is still unclear why oligodendrocytes lose their ability to repair the damage to myelin in the progress of multiple sclerosis (MS). “Interestingly, in collaboration with our Dutch colleagues, we have been able to identify a correlation between levels of sncRNA715 and MBP in the brain tissue of MS patients,” Robin White continues. “In contrast with unaffected areas of the brain in which the myelin structure appears normal, there are higher levels of sncRNA715 in affected areas in which myelin formation is impaired. Our findings may help to provide a molecular explanation for myelination failures in illnesses such as multiple sclerosis.”
The discovery of the molecular pathway that drives the changes seen in the brains of Alzheimer’s patients is reported today, revealing new targets for drug discovery that could be exploited to combat the disease. The study gives the most detailed understanding yet of the complex processes leading to Alzheimer’s.
Alzheimer’s disease is associated with plaques made up of deposits of a molecule called amyloid between brain cells, which leads to the formation of tangles of twisted fibres made from a molecule called tau, found inside the brain cells. This causes the death of brain cells which is thought to bring about the symptoms of memory loss and dementia. Although it has been accepted for over twenty years that the progression of disease is driven by amyloid and results in abnormal changes in tau, the exact mechanisms of disease remain somewhat of a mystery.
Recent genome wide association studies have identified the gene for a molecule called clusterin as a susceptibility factor for late-onset Alzheimer’s disease. Levels of clusterin are also known to be elevated in blood in patients with Alzheimer’s from an early stage in the disease so the researchers wanted to find out what role it might play in the progression of disease.
The team, led by researchers at King’s College London’s Institute of Psychiatry, looked first in mouse brain cells grown in the laboratory and found that the presence of amyloid alters the amount of clusterin in these cells. Clusterin then acts to switch on a signalling pathway that drives the changes in tau that are associated with the formation of tangles inside the cells, another hallmark of the disease. When this signalling pathway was chronically switched on in a mouse model of the disease, the researchers observed an increase in tangle formation and evidence of cognitive defects.
The study, published in the journal Molecular Psychiatry, also looked in humans and detected the signature of clusterin activation in the brains of Alzheimer’s patients but not in the brains of patients with other forms of dementia.
Dr Richard Killick from King’s College London’s Institute of Psychiatry said: “This is the first time we’ve been able to connect the molecular mechanisms behind the formation of amyloid plaques in the brain with the formation of tangles inside the brain cells, two of the defining features of Alzheimer’s disease. Our research has given the most detailed picture yet of how the disease progresses and we hope it will offer leads for the development of new treatments.”
The signalling pathway that is turned on by clusterin is called DKK1-WNT. It involves interactions between a number of different molecules that could prove to be useful targets for the development of new drugs.
Current treatments for Alzheimer’s are focused on alleviating the symptoms and there is no therapy that can prevent the progression of disease.
Professor Simon Lovestone, also from King’s College London’s Institute of Psychiatry, who led the study, said: “We have shown that we can block the toxic effects of amyloid when we stop this signalling pathway in brain cells grown in the lab. We believe that if we could block its activity in the brains of Alzheimer’s patients too, we may have an opportunity to halt the disease in man. Indeed, we have already begun our own drug development programme to do just that and are at the stage where potential compounds are coming back to us for further testing.”
The DKK1-WNT pathways has also been implicated in some human cancers and although there is no evidence for a direct link, the findings from this study mean that there could be an opportunity to make advances in Alzheimer’s research by capitalising on knowledge that is being gained from cancer research, the authors suggest.
Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust, which helped fund this study, said: “We will see more and more people affected by Alzheimer’s disease as our population ages. This study gives us a much-needed additional insight to the complex biology that contributes to the development of Alzheimer’s, which is vital if we are to develop new treatments that are so urgently needed.”
Health professionals may soon have a new method of diagnosing Parkinson’s disease, one that is noninvasive and inexpensive, and, in early testing, has proved to be effective more than 90 percent of the time.
In addition, this new method has the potential to track the progression of Parkinson’s, as well as measure the effectiveness of treatments for the disorder, said Rahul Shrivastav, professor and chairperson of Michigan State University’s Department of Communicative Sciences and Disorders and a member of the team developing the new method.
It involves monitoring a patient’s speech patterns – specifically, movement patterns of the tongue and jaw.
“In Parkinson’s disease, a common limitation is that the movements become slow and have a reduced range,” said Shrivastav. “We believe we see this pattern in speech too – the tongue doesn’t move as far as it should, doesn’t move as quickly as it should and produces subtle changes in speech patterns.”
This method is particularly sensitive to Parkinson’s disease speech and, Shrivastav said, is effective with only two seconds of speech.
“That’s significant in several ways: The detection methodology is noninvasive, easy to administer, inexpensive and capable of being used remotely and in telemedicine applications,” he said.
Presently there are no tried-and-true methods for diagnosing Parkinson’s. Shrivastav said if a person is showing early symptoms of the disease, which include tremors, slower movements or rigid muscles, he or she is given a drug to treat the disease.
“If the symptoms go away,” he said, “then it’s assumed you must have Parkinson’s disease.”
In more advanced cases, he said, symptoms are usually prominent enough that it is fairly easy to diagnose.
Parkinson’s disease is a neurological disorder affecting a half million people in the United States, with 50,000 newly diagnosed cases every year. It occurs when nerve cells in the brain stop producing a chemical called dopamine, which helps control muscle movement. Without dopamine, the nerve cells cannot properly send messages, leading to the loss of muscle function.
While there is no cure for Parkinson’s disease, early detection is particularly important since the treatments currently available for controlling symptoms are most effective at that stage.