Posts tagged science
Articles and news from the latest research reports.
Study explores how brain disruption may foster schizophrenia
Yale University researchers have discovered an innovative way to study how large brain systems are organized, an advance that has already provided insights into diseases such as schizophrenia.
The Yale team used a combination of neuroimaging, computational neurobiology, and pharmacological techniques to reveal functioning at both the cellular level and across larger brain regions.
In a paper in Proceedings of the National Academy of Sciences the week of Sept. 24, Yale scientists use this approach to show that a disruption of a particular signaling mechanisms within larger neural systems may be contribute to schizophrenia symptoms.
Learning requires rhythmical activity of neurons
The hippocampus represents an important brain structure for learning. Scientists at the Max Planck Institute of Psychiatry in Munich discovered how it filters electrical neuronal signals through an input and output control, thus regulating learning and memory processes. Accordingly, effective signal transmission needs so-called theta-frequency impulses of the cerebral cortex. With a frequency of three to eight hertz, these impulses generate waves of electrical activity that propagate through the hippocampus. Impulses of a different frequency evoke no transmission, or only a much weaker one. Moreover, signal transmission in other areas of the brain through long-term potentiation (LTP), which is essential for learning, occurs only when the activity waves take place for a certain while. The scientists even have an explanation for why we are mentally more productive after drinking a cup of coffee or in an acute stress situation: in their experiments, caffeine and the stress hormone corticosterone boosted the activity flow.
Understanding how salamanders grow new limbs provides insights into the potential of human regenerative medicine
By studying a real lizard-like amphibian, which can regenerate missing limbs, the Salk researchers discovered that it isn’t enough to activate genes that kick start the regenerative process. In fact, one of the first steps is to halt the activity of so-called jumping genes.
In research published August 23 in Development, Growth & Differentiation, and July 27 in Developmental Biology, the researchers show that in the Mexican axolotl, jumping genes have to be shackled or they might move around in the genomes of cells in the tissue destined to become a new limb, and disrupt the process of regeneration.
They found that two proteins, piwi-like 1 (PL1) and piwi-like 2 (PL2), perform the job of quieting down jumping genes in this immature tadpole-like form of a salamander, known as an axolotl - a creature whose name means water monster and who can regenerate everything from parts of its brain to eyes, spinal cord, and tail.
"What our work suggests is that jumping genes would be an issue in any situation where you wanted to turn on regeneration," says the studies’ senior author, Tony Hunter, a professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center.
Georgia Tech Creating High-Tech Tools to Study Autism
Researchers in Georgia Tech’s Center for Behavior Imaging have developed two new technological tools that automatically measure relevant behaviors of children, and promise to have significant impact on the understanding of behavioral disorders such as autism.
One of the tools—a system that uses special gaze-tracking glasses and facial-analysis software to identify when a child makes eye contact with the glasses-wearer—was created by combining two existing technologies to develop a novel capability of automatic detection of eye contact. The other is a wearable system that uses accelerometers to monitor and categorize problem behaviors in children with behavioral disorders.
Both technologies already are being deployed in the Center for Behavior Imaging’s (CBI) ongoing work to apply computational methods to screening, measurement and understanding of autism and other behavioral disorders.
Boosting natural marijuana-like brain chemicals treats fragile X syndrome symptoms
UCI study points to role endocannabinoids play in common genetic cause of autism
American and European scientists have found that increasing natural marijuana-like chemicals in the brain can help correct behavioral issues related to fragile X syndrome, the most common known genetic cause of autism.
The work indicates potential treatments for anxiety and cognitive defects in people with this condition. Results appear online in Nature Communications.
Daniele Piomelli of UC Irvine and Olivier Manzoni of INSERM, the French national research agency, led the study, which identified compounds that inhibit enzymes blocking endocannabinoid transmitters called 2-AG in the striatum and cortex regions of the brain.
These transmitters allow for the efficient transport of electrical signals at synapses, structures through which information passes between neurons. In fragile X syndrome, regional synapse communication is severely limited, giving rise to certain cognitive and behavioral problems.
Fragile X syndrome is caused by a mutation of the FMR1 gene on the X chromosome. People born with it are mentally disabled; generally experience crawling, walking and language delays; tend to avoid eye contact; may be hyperactive or impulsive; and have such notable physical characteristics as an elongated face, flat feet and large ears.
The researchers stress that their findings, while promising, do not point to a cure for the condition.
“What we hope is to one day increase the ability of people with fragile X syndrome to socialize and engage in normal cognitive functions,” said Piomelli, a UCI professor of anatomy & neurobiology and the Louise Turner Arnold Chair in the Neurosciences.
The study involved mice genetically altered with FMR1 mutations that exhibited symptoms of fragile X syndrome. Treated with novel compounds that correct 2-AG protein signaling in brain cells, these mice showed dramatic behavioral improvements in maze tests measuring anxiety and open-space acceptance.
While other work has focused on pharmacological treatments for behavioral issues associated with fragile X syndrome, Piomelli noted that this is the first to identify the role endocannabinoids play in the neurobiology of the condition.
About endocannabinoids
Endocannabinoid compounds are created naturally in the body and share a similar chemical structure with THC, the primary psychoactive component of the marijuana plant, Cannabis. Endocannabinoids are distinctive because they link with protein molecule receptors — called cannabinoid receptors — on the surface of cells. For instance, when a person smokes marijuana, the cannabinoid THC activates these receptors. Because the body’s natural cannabinoids control a variety of factors — such as pain, mood and appetite — they’re attractive targets for drug discovery and development. Piomelli is one of the world’s leading endocannabinoid researchers. His groundbreaking work is showing that this system can be exploited by new treatments to combat anxiety, pain, depression and obesity.
(Source: today.uci.edu)
JoVE Article Shows Steps to Isolate Stem Cells from Brain Tumors
A new video protocol in Journal of Visualized Experiments (JoVE) details an assay to identify brain tumor initiating stem cells from primary brain tumors. Through flow cytometry, scientists separate stem cells from the rest of the tumor, allowing quick and efficient analysis of target cells. This approach has been effectively used to identify similar stem cells in leukemia patients.
"Overall, these tumors are extremely rare, with only around one in 100,000 people being diagnosed with a primary brain cancer," Dr. Sheila Singh, co-author and neurosurgeon from McMaster University, explains. "However, these tumors are the second most common malignancy in the pediatric population, and are behind only leukemia as the cancer with the highest mortality rate."
This publication is significant because it allows scientists to identify, purify, and study brain tumor initiating cells rapidly and without sample loss. Because these stem cells allow scientists to grow films in a petri dish, they serve as an effective model of a tumor expanding in the brain of a patient.
Making it easier to make stem cells
The process researchers use to generate induced pluripotent stem cells (iPSCs)—a special type of stem cell that can be made in the lab from any type of adult cell—is time consuming and inefficient. To speed things up, researchers at Sanford-Burnham turned to kinase inhibitors. These chemical compounds block the activity of kinases, enzymes responsible for many aspects of cellular communication, survival, and growth. As they outline in a paper published September 25 in Nature Communications, the team found several kinase inhibitors that, when added to starter cells, help generate many more iPSCs than the standard method. This new capability will likely speed up research in many fields, better enabling scientists around the world to study human disease and develop new treatments.
NYU Biologists Uncover Dynamic Between Biological Clock and Neuronal Activity
Biologists at New York University have uncovered one way that biological clocks control neuronal activity—a discovery that sheds new light on sleep-wake cycles and offers potential new directions for research into therapies to address sleep disorders and jetlag.
“The findings answer a significant question—how biological clocks drive the activity of clock neurons, which, in turn, regulate behavioral rhythms,” explained Justin Blau, an associate professor in NYU’s Department of Biology and the study’s senior author.
Their findings appear in the Journal of Biological Rhythms
Researchers use magnetic pulses to brain to reduce overly optimistic tendencies
Scientists have known for many years that human beings, as a general rule, are an overly optimistic bunch. We close our eyes to statistics suggesting our eating habits may be killing us, ignore warnings about texting while driving and almost always believe things will come out all right in the end if we’ll just hang in there, despite sometimes obvious indications to the contrary. Research has suggested that two specific symmetrically opposite parts of the brain influence our optimism or pessimism, but until now haven’t been able to offer direct proof. Now however, new research by a group of neuroscientists has found, as they describe in their paper published in the Proceedings of the National Academy of Sciences, that turning off one of these areas via magnetic pulses dramatically reduces overly optimistic tendencies.
Parkinson’s Disease Mechanism Identified
Researchers in the Taub Institute at Columbia University Medical Center (CUMC) have identified a mechanism that appears to underlie the common sporadic (non-familial) form of Parkinson’s disease, the progressive movement disorder. The discovery highlights potential new therapeutic targets for Parkinson’s and could lead to a blood test for the disease. The study, based mainly on analysis of human brain tissue, was published in the online edition of Nature Communications.
Studies of rare, familial (heritable) forms of Parkinson’s show that a protein called alpha-synuclein plays a role in the development of the disease. People who have extra copies of the alpha-synuclein gene produce excess alpha-synuclein protein, which can damage neurons. The effect is most pronounced in dopamine neurons, a population of brain cells in the substantia nigra that plays a key role in controlling normal movement and is lost in Parkinson’s. Another key feature of Parkinson’s is the presence of excess alpha-synuclein aggregates in the brain.
As the vast majority of patients with Parkinson’s do not carry rare familial mutations, a key question has been why these individuals with common sporadic Parkinson’s nonetheless acquire excess alpha-synuclein protein and lose critical dopamine neurons, leading to the disease.
Using a variety of techniques, including gene-expression analysis and gene-network mapping, the CUMC researchers discovered how common forms of alpha-synuclein contribute to sporadic Parkinson’s. “It turns out multiple different alpha-synuclein transcript forms are generated during the initial step in making the disease protein; our study implicates the longer transcript forms as the major culprits,” said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and cell biology and neurology at CUMC. “Some very common genetic variants in the alpha-synuclein gene, present in many people, are known to impact the likelihood that an individual will suffer from sporadic Parkinson’s. In our study, we show that people with ‘bad’ variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made and may accumulate in the brain.”
“An unusual aspect of our study is that it is based largely on detailed analysis of actual patient tissue, rather than solely on animal models,” said Dr. Abeliovich. “In fact, the longer forms of alpha-synuclein are human-specific, as are the disease-associated genetic variants. Animal models don’t really get Parkinson’s, which underscores the importance of including the analysis of human brain tissue.”
“Furthermore, we found that exposure to toxins associated with Parkinson’s can increase the abundance of this longer transcript form of alpha-synuclein. Thus, this mechanism may represent a common pathway by which environmental and genetic factors impact the disease,” said Dr. Abeliovich.
The findings suggest that drugs that reduce the accumulation of elongated alpha-synuclein transcripts in the brain might have therapeutic value in the treatment of Parkinson’s. The CUMC team is currently searching for drug candidates and has identified several possibilities.
The study also found elevated levels of the alpha-synuclein elongated transcripts in the blood of a group of patients with sporadic Parkinson’s, compared with unaffected controls. This would suggest that a test for alpha-synuclein may serve as a biomarker for the disease. “There is a tremendous need for a biomarker for Parkinson’s, which now can be diagnosed only on the basis of clinical symptoms. The finding is particularly intriguing, but needs to be validated in additional patient groups,” said Dr. Abeliovich. A biomarker could also speed clinical trials by giving researchers a more timely measure of a drug’s effectiveness.
(Source: cumc.columbia.edu)