Posts tagged psychology

ScienceDaily (Mar. 5, 2012) — Studying tiny bits of genetic material that control protein formation in the brain, Johns Hopkins scientists say they have new clues to how memories are made and how drugs might someday be used to stop disruptions in the process that lead to mental illness and brain wasting diseases.

Neuron (red) accumulates messages (green) when treated with BDNF. (Credit: Image courtesy of Johns Hopkins Medicine)

In a report published in the March 2 issue of Cell, the researchers said certain microRNAs — genetic elements that control which proteins get made in cells — are the key to controlling the actions of so-called brain-derived neurotrophic factor (BDNF), long linked to brain cell survival, normal learning and memory boosting.

During the learning process, cells in the brain’s hippocampus release BDNF, a growth-factor protein that ramps up production of other proteins involved in establishing memories. Yet, by mechanisms that were never understood, BDNF is known to increase production of less than 4 percent of the different proteins in a brain cell.

That led Mollie Meffert, M.D., Ph.D., associate professor of biological chemistry and neuroscience at the Johns Hopkins University School of Medicine to track down how BDNF specifically determines which proteins to turn on, and to uncover the role of regulatory microRNAs.

MicroRNAs are small molecules that bind to and block messages that act as protein blueprints from being translated into proteins. Many microRNAs in a cell shut down protein production, and, conversely, the loss of certain microRNAs can cause higher production of specific proteins.

The researchers measured microRNA levels in brain cells treated with BDNF and compared them to microRNA levels in neurons not treated with BDNF. The researchers noticed that levels of certain microRNAs were lower in brain cells treated with BDNF, suggesting that BDNF controls the levels of these microRNAs and, through this control, also affects protein production. Homing in on those specific microRNAS that disappeared when cells were treated with BDNF, the team found all were of the same type, so-called Let-7 microRNAs, and that all shared a common genetic sequence.

"This short genetic sequence has been shown by other researchers to behave like a bar code that can selectively prevent production of Let-7 microRNAs," says Meffert.

To test if the loss of Let-7 microRNAs lets BDNF increase production of specific proteins, Meffert’s team genetically engineered neurons so they could no longer decrease Let-7 microRNAs. They found that treating these neurons with BDNF no longer resulted in decreased microRNA levels or an increase in learning and memory proteins.

In measuring microRNA levels in cells treated with BDNF, the researchers also found more than 174 microRNAs that increased with BDNF treatment. This suggested to the research team that BNDF treatment also can increase other microRNAs and, thereby, decrease production of certain proteins. Says Meffert, some of these proteins may need to be decreased during learning and memory, whereas others may not contribute to the process at all.

To confirm that BDNF, via microRNA action, halts the production of certain proteins, the researchers monitored living brain cells to find out where messages go in response to BDNF. Messages that aren’t translated into proteins can accumulate inside small formations within cells. Using a microscope, the researchers watched a lab dish containing brain cells that had been marked with a fluorescent molecule that labels these formations as glowing spots. Treating cells with BDNF caused the number and size of the glowing spots to increase. The researchers determined that BDNF uses microRNA to send messages to these spots where they can be exiled away from the translating machinery that turns them into protein.

"Monitoring these fluorescent complexes gave us a window that we needed to understand how BDNF is able to target the production of only certain proteins that help neurons to grow and make learning possible," Meffert says.

Adds Meffert, “Now that we know how BDNF boosts production of learning and memory proteins, we have an opportunity to explore whether therapeutics can be designed to enhance this mechanism for treatment of patients with mental disorders and neurodegenerative diseases like Alzheimer’s disease.”

Source: Science Daily

March 4, 2012 

Brain diagram. Credit: dwp.gov.uk

Opening the door to the development of thought-controlled prosthetic devices to help people with spinal cord injuries, amputations and other impairments, neuroscientists at the University of California, Berkeley, and the Champalimaud Center for the Unknown in Portugal have demonstrated that the brain is more flexible and trainable than previously thought.

Their new study, to be published Sunday, March 4, in the advanced online publication of the journal Nature, shows that through a process called plasticity, parts of the brain can be trained to do something it normally does not do. The same brain circuits employed in the learning of motor skills, such as riding a bike or driving a car, can be used to master purely mental tasks, even arbitrary ones.

Over the past decade, tapping into brain waves to control disembodied objects has moved out of the realm of parlor tricks and parapsychology and into the emerging field of neuroprosthetics. This new study advances work by researchers who have been studying the brain circuits used in natural movement in order to mimic them for the development of prosthetic devices.

"What we hope is that our new insights into the brain’s wiring will lead to a wider range of better prostheses that feel as close to natural as possible," said Jose Carmena, UC Berkeley associate professor of electrical engineering, cognitive science and neuroscience. "They suggest that learning to control a BMI (brain-machine interface), which is inherently unnatural, may feel completely normal to a person, because this learning is using the brain’s existing built-in circuits for natural motor control."

Carmena and co-lead author Aaron Koralek, a UC Berkeley graduate student in Carmena’s lab, collaborated on this study with Rui Costa, co-principal investigator of the study and principal investigator at the Champalimaud Neuroscience Program, and co-lead author Xin Jin, a post-doctoral fellow in Costa’s lab.

Previous studies have failed to rule out the role of physical movement when learning to use a prosthetic device.

"This is key for people who can’t move," said Carmena, who is also co-director of the UC Berkeley-UCSF Center for Neural Engineering and Prostheses. "Most brain-machine interface studies have been done in healthy, able-bodied animals. What our study shows is that neuroprosthetic control is possible, even if physical movement is not involved." 

To clarify these issues, the scientists set up a clever experiment in which rats could only complete an abstract task if overt physical movement was not involved. The researchers decoupled the role of the targeted motor neurons needed for whisker twitching with the action necessary to get a food reward.

The rats were fitted with a brain-machine interface that converted brain waves into auditory tones. To get the food reward – either sugar-water or pellets – the rats had to modulate their thought patterns within a specific brain circuit in order to raise or lower the pitch of the signal.

Auditory feedback was given to the rats so that they learned to associate specific thought patterns with a specific pitch. Over a period of just two weeks, the rats quickly learned that to get food pellets, they would have to create a high-pitched tone, and to get sugar water, they needed to create a low-pitched tone.

If the group of neurons in the task were used for their typical function – whisker twitching – there would be no pitch change to the auditory tone, and no food reward.

"This is something that is not natural for the rats," said Costa. "This tells us that it’s possible to craft a prosthesis in ways that do not have to mimic the anatomy of the natural motor system in order to work."

The study was also set up in a way that demonstrated intentional, as opposed to habitual, behavior. The rats were able to vary the amount of pellets or sugar water received based upon their own level of hunger or thirst.

"The rats were aware; they knew that controlling the pitch of the tone was what gave them the reward, so they controlled how much sugar water or how many pellets to take, when to do it, and how to do it in absence of any physical movement," said Costa.

Researchers hope these findings will lead to a new generation of prosthetic devices that feel natural.

"We don’t want people to have to think too hard to move a robotic arm with their brain," said Carmena.

Provided by University of California - Berkeley 

Source: medicalxpress.com

This undated handout artist rendering provided by the Schneider Lab, University of Pittsburgh shows an experimental type of scan showing damage to the brain’s nerve fibers after a traumatic brain injury. The yellow shows missing fibers on one side of the brain, as compared to the uninjured side in green, in a man left with limited use of his left arm and hand. The soldier on the fringes of an explosion. The survivor of a car wreck. The football player who took yet another skull-rattling hit. Too often, only time can tell when a traumatic brain injury will leave lasting harm _ there’s no good way to diagnose the damage. Now scientists are testing a tool that promises to light up breaks that these injuries leave in the brain’s wiring, much like X-rays show broken bones. (AP Photo/Schneider Lab, University of Pittsburgh)

The soldier on the fringes of an explosion. The survivor of a car wreck. The football player who took yet another skull-rattling hit. Too often, only time can tell when a traumatic brain injury will leave lasting harm - there’s no good way to diagnose the damage.

Now scientists are testing a tool that lights up the breaks these injuries leave deep in the brain’s wiring, much like X-rays show broken bones.

Research is just beginning in civilian and military patients to learn if this new kind of MRI-based test really could pinpoint their injuries and one day guide rehabilitation. It’s an example of the hunt for better brain scans, maybe even a blood test, to finally tell when a blow to the head causes damage that today’s standard testing simply can’t see.

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ScienceDaily (Mar. 2, 2012) — A powerful new imaging technique called High Definition Fiber Tracking (HDFT) will allow doctors to clearly see for the first time neural connections broken by traumatic brain injury (TBI) and other neurological disorders, much like X-rays show a fractured bone, according to researchers from the University of Pittsburgh in a report published online in the Journal of Neurosurgery.

High definition fiber-tracking map of a million brain fibers. (Credit: Walt Schneider Laboratory)

In the report, the researchers describe the case of a 32-year-old man who wasn’t wearing a helmet when his all-terrain vehicle crashed. Initially, his CT scans showed bleeding and swelling on the right side of the brain, which controls left-sided body movement. A week later, while the man was still in a coma, a conventional MRI scan showed brain bruising and swelling in the same area. When he awoke three weeks later, the man couldn’t move his left leg, arm and hand.

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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.

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(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