Posts tagged science

ScienceDaily (Mar. 2, 2012) — Impaired social function is a cardinal symptom of autism spectrum disorders (ASDs). One of the brain circuits that enable us to relate to other people is the “mirror neuron” system. This brain circuit is activated when we watch other people, and allows our brains to represent the actions of others, influencing our ability to learn new tasks and to understand the intentions and experiences of other people.

This mirror neuron system is impaired in individuals with ASD and better understanding the neurobiology of this system could help in the development of new treatments.

In their new study, Dr. Peter Enticott at Monash University and his colleagues used transcranial magnetic stimulation to stimulate the brains of individuals with ASD and healthy individuals while they observed different hand gestures. This allowed the researchers to measure the activity of each individual’s mirror neuron system with millisecond precision in response to each observed action.

They found that the individuals with ASD showed a blunted brain response to stimulation of the motor cortex when viewing a transitive hand gesture. In other words, the mirror neuron system in the ASD individuals became less activated when watching the gestures, compared to the healthy group. In addition, among people with ASD, less mirror neuron activity was associated with greater social impairments. This finding adds to the evidence that deficits in mirror neuron system functioning contribute to the social deficits in ASD.

This finding also directly links a specific type of brain dysfunction in people with autism spectrum disorder to a specific symptom. This is important because “we do not have a substantial understanding of the brain basis of autism spectrum disorder, or a validated biomedical treatment for the disorder,” said Dr. Enticott. “If we can develop a substantial understanding of the biology of specific symptoms, this will allow us to develop treatments targeted specifically to the symptoms.”

"This study is an example of the effort to break down the component problems associated with autism spectrum disorder and to map these problems on to particular brain circuits," commented Dr. John Krystal, editor of Biological Psychiatry.

Enticott added, “We are currently investigating whether non-invasive brain stimulation can be used to improve mirror neuron activity in autism spectrum disorder, which would have substantial potential therapeutic implications.”

Source: Science Daily

ScienceDaily (Mar. 2, 2012) — Millions of people suffer from Parkinson’s disease, a disorder of the nervous system that affects movement and worsens over time. As the world’s population ages, it’s estimated that the number of people with the disease will rise sharply. Yet despite several effective therapies that treat Parkinson’s symptoms, nothing slows its progression.

Artist’s rendering of neurons. (Credit: iStockphoto)

While it’s not known what exactly causes the disease, evidence points to one particular culprit: a protein called α-synuclein. The protein, which has been found to be common to all patients with Parkinson’s, is thought to be a pathway to the disease when it binds together in “clumps,” or aggregates, and becomes toxic, killing the brain’s neurons.

Now, scientists at UCLA have found a way to prevent these clumps from forming, prevent their toxicity and even break up existing aggregates.

UCLA professor of neurology Jeff Bronstein and UCLA associate professor of neurology Gal Bitan, along with their colleagues, report the development of a novel compound known as a “molecular tweezer,” which in a living animal model blocked α-synuclein aggregates from forming, stopped the aggregates’ toxicity and, further, reversed aggregates in the brain that had already formed. And the tweezers accomplished this without interfering with normal brain function.

Read more …

(Medical Xpress) — As scientists struggle to find an effective way to prevent Alzheimer’s disease, researchers at the University of Wisconsin School of Medicine and Public health may have found a new approach to interrupting the process that leads to the devastating disease.

The image shows that the enzymes ATase1 and ATase2 are abundantly present in the brains of Alzheimer’s disease patients. The green color labels the ATases while the blue labels the nuclei. Both neurons and glial cells are shown.

Building on their knowledge of two enzymes that control an “uber” enzyme critical to the development of the disease, the scientists found that the two enzymes are present in the brains of Alzheimer’s patients. And by screening some 15,000 compounds, they discovered two that lower activity of the enzymes in test tubes. 

Read more …

Article Date: 02 Mar 2012 - 1:00 PST

Scientists from Seattle Children’s Research Institute and the University of Washington, in collaboration with the Genomic Disorders Group Nijmegen in the Netherlands, have identified two new genes that cause Baraitser-Winter syndrome, a rare brain malformation that is characterized by droopy eyelids and intellectual disabilities.

“This new discovery brings the total number of genes identified with this type of brain defect to eight,” said William Dobyns, MD, a geneticist at Seattle Children’s Research Institute. Identification of the additional genes associated with the syndrome make it possible for researchers to learn more about brain development. The study, “De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome,” was published online in Nature Genetics.

The brain defect found in Baraitser-Winter syndrome is a smooth brain malformation or “lissencephaly,” as whole or parts of the surface of the brain appear smooth in scans of patients with the disorder. Previous studies by Dr. Dobyns and other scientists identified six genes that cause the smooth brain malformation, accounting for approximately 80% of affected children. Physicians and researchers worldwide have identified to date approximately 20 individuals with Baraitser-Winter syndrome.

While the condition is rare, Dr. Dobyns said the team’s findings have broad scientific implications. “Actins, or the proteins encoded by the ACTB and ACTG1 genes, are among the most important proteins in the function of individual cells,” he said. “Actins are critical for cell division, cell movement, internal movement of cellular components, cell-to-cell contact, signaling and cell shape,” said Dr. Dobyns, who is also a University of Washington professor of pediatrics. “The defects we found occur in the only two actin genes that are expressed in most cells,” he said. Gene expression is akin to a “menu” for conditions like embryo development or healing from an injury. The correct combination of genes must be expressed at the right time to allow proper development. Abnormal expression of genes can lead to a defect or malformation.

“Birth defects associated with these two genes also seem to be quite severe,” said Dr. Dobyns. “Children and people with these genes have short stature, an atypical facial appearance, birth defects of the eye, and the smooth brain malformation along with moderate mental retardation and epilepsy. Hearing loss occurs and can be progressive,” he said.

Dr. Dobyns is a renowned researcher whose life-long work has been to try to identify the causes of children’s developmental brain disorders such as Baraitser-Winter syndrome. He discovered the first known chromosome abnormality associated with lissencephaly (Miller-Dieker syndrome) while still in training in child neurology at Texas Children’s Hospital in 1983. That research led, 10 years later, to the discovery by Dobyns and others of the first lissencephaly gene known as LIS1.

Source: Medical News Today  

ScienceDaily (Mar. 1, 2012) — The association of the inhaled anesthetic isoflurane with Alzheimer’s-disease-like changes in mammalian brains may by caused by the drug’s effects on mitochondria, the structures in which most cellular energy is produced. In a study that will appear in Annals of Neurology and has received early online release, Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory — a result not seen when another anesthetic, desflurane, was administered. They also found evidence that the two drugs have significantly different effects on mitochondrial function.

"These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria," says Yiying (Laura) Zhang, MD, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study’s lead author. "This work needs to be confirmed in human studies, but it’s looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer’s patients."

Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer’s, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period. In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer’s-like changes — increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease — in the brains of mice. The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane’s effects with those of desflurane, another common anesthetic that has not been associated with neuronal damage.

In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase. The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species — unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group. None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.

In another study by members of the same research team — appearing in the February issue of Anesthesia and Analgesia and published online in November — about a quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance. That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients — 15 in each treatment group — so its results need to be confirmed in significantly larger groups.

"Approximately 8.5 million Alzheimer’s disease patients worldwide will need anesthesia and surgical care every year," notes Zhongcong Xie, MD, PhD, corresponding author of both studies and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine. "Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in anesthesia, neurology, geriatric medicine and other specialties. As the first step, we need to identify anesthetics that are less likely to contribute to Alzheimer’s disease neuropathogenesis and cognitive dysfunction." Xie is an associate professor of Anesthesia at Harvard Medical School (HMS)

Source: Science Daily

ScienceDaily (Mar. 1, 2012) — Down syndrome (DS) is the most common genetic disorder in live born children arising as a consequence of a chromosomal abnormality. It occurs as a result of having three copies of chromosome 21, instead of the usual two. It causes substantial physical and behavioral abnormalities, including life-long cognitive dysfunction that can range from mild to severe but which further deteriorates as individuals with DS age.

It is not currently possible to effectively treat the cognitive impairments associated with DS. However, these deficits are an increasing focus of research. In this issue of Biological Psychiatry, researchers at Stanford University, led by Dr. Ahmad Salehi, have published a review which highlights potential strategies for the treatment of these cognitive deficits.

The authors focus on insights emerging from animal models of Down syndrome and outline the structural abnormalities in the DS brain. They also discuss studies that have linked the over-expression of the amyloid precursor protein gene, called APP, to the degeneration of neurons in mice. These findings have led to the development of therapeutic treatments in mice, which now must be tested in humans.

"For more than a decade, we have been working on identifying a strategy to treat cognitive disabilities in our Down syndrome mouse models," said Dr. Salehi. "Considering the research and results with mouse models as an indication of success of a strategy in humans, we are ever closer to finding ways to at least partially restore cognitive function in children and adults with Down syndrome."

Interestingly, this research is also providing insights into Alzheimer’s disease (AD), the archetypal disorder of late life. All adults with Down syndrome develop AD pathology by age 40, and there are some remarkable similarities in the brain degeneration and cognitive dysfunction of individuals with DS and those with AD.

The leading AD hypothesis posits that it is caused by increasingly elevated levels of amyloid-related proteins, which are toxic to nerve cells in the brain. These same proteins also accumulate in the brains of people with DS because they are made by the APP gene, which is located on chromosome 21. Individuals with AD don’t have the extra chromosome, of course; rather, it is mutations in APP that appear to cause the brain degeneration associated with AD.

Dr. John Krystal, editor of Biological Psychiatry, commented: “The convergence of research on Down syndrome and Alzheimer’s disease highlights a central point that cannot be overstated. When we understand the fundamental biology of the brain, important new conceptual bridges emerge that guide new treatment approaches.”

Salehi added, “In the near future, we may very likely look back with the perspective that Down syndrome represents an example of how families of affected individuals came together and by supporting basic research, changed the course of a disorder that was considered untreatable for more than a century.”

Source: Science Daily

ScienceDaily (Mar. 1, 2012) — Despite the promise associated with the therapeutic use of human stem cells, a complete understanding of the mechanisms that control the fundamental question of whether a stem cell becomes a specific cell type within the body or remains a stem cell has-until now-eluded scientists.

A University of Georgia study published in the March 2 edition of the journal Cell Stem Cell, however, creates the first ever blueprint of how stem cells are wired to respond to the external signaling molecules to which they are constantly exposed. The finding, which reconciles years of conflicting results from labs across the world, gives scientists the ability to precisely control the development, or differentiation, of stem cells into specific cell types.

"We can use the information from this study as an instruction book to control the behavior of stem cells," said lead author Stephen Dalton, Georgia Research Alliance Eminent Scholar of Molecular Biology and professor of cellular biology in the UGA Franklin College of Arts and Sciences. "We’ll be able to allow them to differentiate into therapeutic cell types much more efficiently and in a far more controlled manner."

The previous paradigm held that individual signaling molecules acted alone to set off a linear chain of events that control the fate of cells. Dalton’s study, on the other hand, reveals that a complex interplay of several molecules controls the “switch” that determines whether a stem cell stays in its undifferentiated state or goes on to become a specific cell type, such as a heart, brain or pancreatic cell.

"This work addresses one of the biggest challenges in stem cell research-figuring out how to direct a stem cell toward becoming a specific cell type," said Marion Zatz, who oversees stem cell biology grants at the National Institutes of Health’s National Institute of General Medical Sciences, which partially supported the work.

"In this paper, Dr. Dalton puts together several pieces of the puzzle and offers a model for understanding how multiple signaling pathways coordinate to steer a stem cell toward differentiating into a particular type of cell. This framework ultimately should not only advance a fundamental understanding of embryonic development, but facilitate the use of stem cells in regenerative medicine."

To get a sense of how murky the understanding of stem cell differentiation was, consider that previous studies reached opposite conclusions about the role of a common signaling molecule known as Wnt. About half the published studies found that Wnt kept a molecular switch in an “off” position, which kept the stem cell in its undifferentiated, or pluripotent, state. The other half reached the opposite conclusion.

Could the same Wnt molecule be responsible for both outcomes? As it turns out, the answer is yes. Dalton’s team found that in small amounts, Wnt signaling keeps the stem cell in its pluripotent state. In larger quantities, it does the opposite and encourages the cell to differentiate.

But Wnt doesn’t work alone. Other molecules, such as insulin-like growth factor (Igf), fibroblast growth factor (Fgf2) and Activin A also play a role. To complicate things further, these signaling molecules amplify each other so that a two-fold increase in one can result in a 10-fold increase in another. The timing with which the signals are introduced matters, too.

"One of the things that surprised us was how all of the pathways ‘talk’ to each other," Dalton said. "You can’t do anything to the Igf pathway without affecting the Fgf2 pathway, and you can’t do anything to Fgf2 without affecting Wnt. It’s like a house of cards; everything is totally interconnected."

Dalton and his team spent a painstaking five years creating hypotheses about the how the signaling molecules function, testing those hypotheses, and-when faced with an unexpected result-rebuilding their hypotheses and re-testing. This process continued until the entire system was resolved.

Their finding gives scientists a more complete understanding of the first step that stem cells take as they differentiate, and Dalton is confident that the same approach can be used to understand subsequent developmental steps that occur as the cells in an embryo divide into ever-more specific cell types.

"Hopefully this type of approach will give us a greater understanding of cells and how they can be manipulated so that we can progress much more rapidly toward the routine use of stem cells in therapeutic settings," Dalton said.

The research was funded by the National Institute of Child Health and Human Development and the National Institute of General Medical Sciences.

Source: Science Daily

(Medical Xpress) — Researchers from Western University have utilized their own game-changing technology – previously developed for use with patients in a vegetative state – to assess a more prevalent group of brain-injured patients, those in the minimally conscious state (MCS). Their findings were released today in Neurology, the medical journal of the American Academy of Neurology.

The study, led by Adrian Owen, Canada Excellence Research Chair in Cognitive Neuroscience and Imaging, and Damian Cruse of Western’s Brain and Mind Institute, is a follow-up to the team’s groundbreaking Lancet publication from November 2011 that used electroencephalography (EEG) to show that some vegetative state patients were able to reliably follow commands, even though this ability was entirely undetectable from their external behaviour. 

In the new paper, titled “The relationship between aetiology and covert cognition in the minimally-conscious state,” the MCS patients showed some inconsistent but reproducible external signs of awareness, such as being able to follow their eyes in a mirror.  Cruse says, however, that currently very little is known about their ‘internal’ state of awareness that may be hidden from their external behaviour. 

"Using our EEG approach, we found that 22 per cent of 23 MCS patients were able to complete a complex task which required them to imagine particular types of movement," says Cruse, a Post-Doctoral Fellow at the Brain and Mind Institute and the lead writer of the paper. "This tells us that these patients have a much higher level of cognitive ability than what you could detect from their behaviour."

Cruse adds that the cause of the brain injury was a determining factor in finding these cognitive abilities as 33 per cent of traumatically injured patients (e.g. traffic accident, fall) returned positive EEG results compared to zero per cent of non-traumatically injured patients (e.g. heart attack, stroke).

The research team, in collaboration with Steven Laureys at the University of Liège, Belgium, asked patients approximately 100 times each to imagine moving his or her right-hand and toes. By making recordings of the patients’ EEG, a measure of the electrical activity of the brain, the team showed that 22 per cent of the MCS patients were able to produce patterns of brain activity that were indistinguishable from a healthy individual following the same commands. 

"There are a large number of patients in the MCS worldwide, and our approach highlights the importance of using EEG and other forms of brain imaging when assessing the mental capabilities of patients following brain injury," says Cruse "It reinforces our understanding that the externally observable abilities of a patient are not necessarily a true reflection of their internal state."

Provided by University of Western Ontario

Source: medicalxpress.com

A major downside of the medical use of marijuana is the drug’s ill effects on working memory, the ability to transiently hold and process information for reasoning, comprehension and learning. Researchers reporting in the March 2 print issue of the Cell Press journal Cell provide new insight into the source of those memory lapses. The answer comes as quite a surprise: Marijuana’s major psychoactive ingredient (THC) impairs memory independently of its direct effects on neurons. The side effects stem instead from the drug’s action on astroglia, passive support cells long believed to play second fiddle to active neurons.

The findings offer important new insight into the brain and raise the possibility that marijuana’s benefits for the treatment of pain, seizures and otherailments might some day be attained without hurting memory, the researchers say.

With these experiments in mice, “we have found that the starting point for this phenomenon – the effect of marijuana on working memory – is the astroglialcells,” said Giovanni Marsicano of INSERM in France.

"This is the first direct evidence that astrocytes modulate working memory," added Xia Zhang of the University of Ottawa in Canada.

The new findings aren’t the first to suggest astroglia had been given short shrift. Astroglial cells (also known as astrocytes) have been viewed as cells that support, protect and feed neurons for the last 100 to 150 years, Marsicano explained. Over the last decade, evidence has accumulated that these cells play a more active role in forging the connections from one neuron to another.

The researchers didn’t set out to discover how marijuana causes its cognitive side effects. Rather, they wanted to learn why receptors that respond to both THC and signals naturally produced in the brain are found on astroglial cells. These cannabinoid type-1 (CB1R) receptors are very abundant in the brain, primarily on neurons of various types.

Zhang and Marsicano now show that mice lacking CB1Rs only on astroglial cells of the brain are protected from the impairments to spatial working memory that usually follow a dose of THC. In contrast, animals lacking CB1Rs in neurons still suffer the usual lapses. Given that different cell types express different variants of CB1Rs, there might be a way to therapeutically activate the receptors on neurons while leaving the astroglial cells out, Marsicano said.

"The study shows that one of the most common effects of cannabinoid intoxication is due to activation of astroglial CB1Rs," the researchers wrote.

The findings further suggest that astrocytes might be playing unexpected roles in other forms of memory in addition to spatial working memory, Zhang said.

The researchers hope to explore the activities of endogenous endocannabinoids, which naturally trigger CB1Rs, on astroglial and other cells. The endocannabinoid system is involved in appetite, pain, mood, memory and many other functions. “Just about any physiological function you can think of in the body, it’s likely at some point endocannabinoids are involved,” Marsicano said.

And that means an understanding of how those natural signaling molecules act on astroglial and other cells could have a real impact. For instance, Zhang said, “we may find a way to deal with working memory problems in Alzheimer’s.”

Source: medicalxpress.com

(PhysOrg.com) — Geraldo Barbosa, professor of electrical engineering and computer science at Northwestern University has posed an interesting challenge. He wonders if the human eye and brain together are capable of actually seeing entangled images. This is not a philosophical question, as he has phrased the query as part of a practical experiment that someone with the proper lab could actually carry out. To that end, he’s posted a paper on the preprint server arXiv with the hope that a physics team will take up the challenge.

The whole idea is based on entanglement and the means by which researchers make it come about. What they do is shoot a laser at a non-linear crystal causing the photons in the beam to be converted into lower frequency entangled pairs. Those pairs are then directed to sensors which individually are able to measure a fuzzy or blurred “image”. But when both of the entangled photons are taken together as a single measurement, the image sharpens. These images are of course far too small for the human eye to see, plus they don’t last long enough for them to be seen anyway. To address these issues, researchers have taken to firing lasers that are formed into patterns such as a doughnut shape in a continuous sequence. The result is a steady stream of entangled pairs being created in the shape of a doughnut.

Barbosa wants to know what would happen if instead of forming a doughnut shape, the lasers were made to look like a letter in the alphabet, such as the letter A, and then of course if it were made large enough to be seen by the human eye. Two entangled letter As should be created and seeable albeit in a lower frequency. If that happened, would the human eye when paired with the brain’s abilities, be able to merge the two into a sharp readable image, or would we see just the individual blurred images captured by just one sensor?

Barbosa doesn’t know, and neither does anyone else, thus he suggests someone or some group build an experiment to find out.

The ability to see things differently than we are accustomed to seeing isn’t anything new of course. Some animals can see things in the infrared spectrum for example and evidence has been slowly emerging as described here, here and here, suggesting that some migrating birds are able to “see” the Earth’s magnetic field. So maybe it’s possible that we see entangled images every day, and just don’t know it.

Hopefully someone will take Barbosa up on his challenge, and then we’ll all find out if it’s possible or not.

More information: Can humans see beyond intensity images? by Geraldo A. Barbosa, arXiv:1202.5434v1 [q-bio.NC] http://arxiv.org/abs/1202.5434

Source: PHYSORG.com