Posts Tagged ‘research’

\

by DAVID NIELD

A specific part of the brain called the caudate nucleus could control pessimistic responses, according to animal tests, a finding which might help us unlock better treatments for mental disorders like anxiety and depression.

These disorders often come with negative moods triggered by a pessimistic reaction, and if scientists can figure out how to control that reaction, we might stand a better chance of dealing with the neuropsychiatric problems that affect millions of people worldwide – and maybe discover the difference between glass half full and glass half empty people along the way.

The research team from MIT found that when the caudate nucleus was artificially stimulated in macaques, the animals were more likely to make negative decisions, and consider the potential drawback of a decision rather than the potential benefit.

This pessimistic decision-making continued right through the day after the original stimulation, the researchers found.

“We feel we were seeing a proxy for anxiety, or depression, or some mix of the two,” says lead researcher Ann Graybiel. “These psychiatric problems are still so very difficult to treat for many individuals suffering from them.”

The caudate nucleus has previously been linked to emotional decision-making, and the scientists stimulated it with a small electrical current while the monkeys were offered a reward (juice) and an unpleasant experience (a puff of air to the face) at the same time.

In each run through the amount of juice and the strength of the air blast varied, and the animals could choose whether or not to accept the reward – essentially measuring their ability to weigh up the costs of an action against the benefits.

When the caudate nucleus was stimulated, this decision-making got skewed, so the macaques started rejecting juice/air ratios they would have previously accepted. The negative aspects apparently began to seem greater, while the the rewards became devalued.

“This state we’ve mimicked has an overestimation of cost relative to benefit,” says Graybiel. After a day or so, the effects gradually disappeared.

The researchers also found brainwave activity in the caudate nucleus, part of the basal ganglia, changed when decision-making patterns changed. This might give doctors a marker to indicate whether someone would be responsive to treatment targeting this part of the brain or not.

The next stage is to see whether the same effect can be noticed in human beings – scientists have previously linked abnormal brain activity in people with mood disorders to regions connected to the caudate nucleus, but there’s a lot more work to be done to confirm these neural connections.

Making progress isn’t easy because of the incredibly complexity of the brain, but the researchers think their results show the caudate nucleus could be disrupting dopamine activity in the brain, controlling mood and our sense of reward and pleasure.

“There must be many circuits involved,” says Gabriel. “But apparently we are so delicately balanced that just throwing the system off a little bit can rapidly change behaviour.”

The research has been published in Neuron.

https://www.sciencealert.com/we-found-the-brain-region-for-pessimism

Advertisements

By Timothy Roberts

Being able to recall memories, whether short-term or long-term is something that we all need in life. It comes in handy when we are studying at school or when we are trying to remember where we left our keys. We also tend to use our memory at work and remembering somebody’s name is certainly a good thing.

Although many of us may consider ourselves to have a good memory, we are all going to forget things from time to time. When it happens, we might feel as if we are slipping but there may be more behind it than you realize.

Imagine this scenario; you go to the grocery store to pick up 3 items and suddenly, you forget why you were there. Even worse, you may walk from one room to another and forget why you got up in the first place!

If you often struggle with these types of problems, you will be happy to learn that there is probably nothing wrong with you. In fact, a study that was done by the Neuron Journal and it has some rather good news. It says that forgetting is part of the brain process that might actually make you smarter by the time the day is over.

Professors took part in a study at the University of Toronto and they discovered that the perfect memory actually doesn’t necessarily reflect your level of intelligence.

You might even be surprised to learn that when you forget details on occasion, it can make you smarter.

Most people would go by the general thought that remembering more means that you are smarter.

According to the study, however, when you forget a detail on occasion, it’s perfectly normal. It has to do with remembering the big picture compared to remembering little details. Remembering the big picture is better for the brain and for our safety.

Our brains are perhaps more of a computer than many of us think. The hippocampus, which is the part of the brain where memories are stored, tends to filter out the unnecessary details.

In other words, it helps us to “optimize intelligent decision making by holding onto what’s important and letting go of what’s not.”

Think about it this way; is it easier to remember somebody’s face or their name? Which is the most important?

In a social setting, it is typically better to remember both but if we were part of the animal kingdom, remembering somebody as being a threat would mean our very lives. Remembering their name would be inconsequential.

The brain doesn’t automatically decide what we should remember and what we shouldn’t. It holds new memories but it sometimes overwrites old memories.

When the brain becomes cluttered with memories, they tend to conflict with each other and that can make it difficult to make important decisions.

That is why the brain tends to hold on to those big picture memories but they are becoming less important with the advent of technology.

As an example, at one time, we would have learned how to spell words but now, we just use Google if we don’t know how to spell them. We also tend to look everything up online, from how to change a showerhead to how to cook meatloaf for dinner.

If you forget everything, you may want to consider having a checkup but if you forget things on occasion, it’s perfectly okay.

The moral of the story is, the next time you forget something, just think of it as your brain doing what it was designed to do.

http://wetpaintlife.com/scientists-say-that-being-forgetful-is-actually-a-sign-you-are-unusually-intelligent/?utm_source=vn&utm_tracking=11&utm_medium=Social

Methyl chemical groups dot lengths of DNA, helping to control when certain genes are accessible by a cell. In new research, UCLA scientists have shown that at the connections between brain cells—which often are located far from the central control centers of the cells—methyl groups also dot chains of RNA. This methyl markup of RNA molecules is likely key to brain cells’ ability to quickly send signals to other cells and react to changing stimuli in a fraction of a second.

To dictate the biology of any cell, DNA in the cell’s nucleus must be translated into corresponding strands of RNA. Next, the messenger RNA, or mRNA—an intermediate genetic molecule between DNA and proteins—is transcribed into proteins. If a cell suddenly needs more of a protein—to adapt to an incoming signal, for instance—it must translate more DNA into mRNA. Then it must make more proteins and shuttle them through the cell to where they are needed. This process means that getting new proteins to a distant part of a cell, like the synapses of neurons where signals are passed, can take time.

Research has recently suggested that methyl chemical groups, which can control when DNA is transcribed into mRNA, are also found on strands of mRNA. The methylation of mRNA, researchers hypothesize, adds a level of control to when the mRNA can be translated into proteins, and their occurrence has been documented in a handful of organs throughout the bodies of mammals. The pattern of methyls on mRNA in any given cell is dubbed the “epitranscriptome.”

UCLA and Kyoto University researchers mapped out the location of methyls on mRNA found at the synapses, or junctions, of mouse brain cells. They isolated brain cells from adult mice and compared the epitranscriptome found at the synapses to the epitranscriptomes of mRNA elsewhere in the cells. At more than 4,000 spots on the genome, the mRNA at the synapse was methylated more often. More than half of these spots, the researchers went on to show, are in genes that encode proteins found mostly at the synapse. The researchers found that when they disrupted the methylation of mRNA at the synapse, the brain cells didn’t function normally.

The methylation of mRNA at the synapse is likely one of many ways that neurons speed up their ability to send messages, by allowing the mRNA to be poised and ready to translate into proteins when needed.

The levels of key proteins at synapses have been linked to a number of psychiatric disorders, including autism. Understanding how the epitranscriptome is regulated, and what role it plays in brain biology, may eventually provide researchers with a new way to control the proteins found at synapses and, in turn, treat disorders characterized by synaptic dysfunction.

More information: Daria Merkurjev et al. Synaptic N6-methyladenosine (m6A) epitranscriptome reveals functional partitioning of localized transcripts, Nature Neuroscience (2018). DOI: 10.1038/s41593-018-0173-6

Read more at: https://phys.org/news/2018-08-methyl-rna-key-brain-cell.html#jCp


Low responsibility aversion is an important determinant of the decision to lead.

Leaders are more willing to take responsibility for making decisions that affect the welfare of others. In a new study, researchers at the University of Zurich identified the cognitive and neurobiological processes that influence whether someone is more likely to take on leadership or to delegate decision-making.

Parents, company bosses and army generals, as well as teachers and heads of state, all have to make decisions that affect not only themselves, but also influence the welfare of others. Sometimes, the consequences will be borne by individuals, but sometimes by whole organizations or even countries.

Researchers from the Department of Economics investigated what distinguishes people with high leadership abilities. In the study, which has just been published in the journal Science, they identify a common decision process that may characterize followers: Responsibility aversion, or the unwillingness to make decisions that also affect others.

Controlled experiments and brain imaging

In the study, leaders of groups could either make a decision themselves or delegate it to the group. A distinction was drawn between “self” trials, in which the decision only affected the decision-makers themselves, and “group” trials, in which there were consequences for the whole group. The neurobiological processes taking place in the brains of the participants as they were making the decisions were examined using functional magnetic resonance imaging (fMRI).

The scientists tested several common intuitive beliefs, such as the notion that individuals who are less afraid of potential losses or taking risks, or who like being in control, will be more willing to take on responsibility for others. These characteristics, however, did not explain the differing extent of responsibility aversion found in the study participants. Instead, they found that responsibility aversion was driven by a greater need for certainty about the best course of action when the decision also had an effect on others. This shift in the need for certainty was particularly pronounced in people with a strong aversion to responsibility.

“Because this framework highlights the change in the amount of certainty required to make a decision, and not the individual’s general tendency for assuming control, it can account for many different leadership types,” says lead author Micah Edelson. “These can include authoritarian leaders who make most decisions themselves, and egalitarian leaders who frequently seek a group consensus.”

More information: Computational and neurobiological foundations of leadership decisions. Science: August 2, 2018. DOI: 10.1126/science.aat0036


Lung cancer seen on chest X ray.

Researchers have identified a gene that when inhibited or reduced, in turn, reduced or prevented human non-small cell lung cancer tumors from growing.

When mice were injected with non-small cell lung cancer cells that contained the gene NOVA1, three of four mice formed tumors. When the mice were injected with cancer cells without NOVA1, three of four mice remained tumor-free.

The fourth developed a tumor, but it was very small compared to the mice with the NOVA1 tumor cells, said Andrew Ludlow, first author on the study and assistant professor at the University of Michigan School of Kinesiology.

The research appears online today in Nature Communications. Ludlow did the work while a postdoctoral fellow at the University of Texas Southwestern Medical Center, in the shared lab of Woodring Wright, professor of cell biology and internal medicine, and Jerry Shay, professor of cell biology.

The study found that in cancer cells, the NOVA1 gene is thought to activate telomerase, the enzyme that maintains telomeres—the protective caps on the ends of chromosomes that preserve genetic information during cell division (think of the plastic aglets that prevent shoelace ends from fraying).

Telomerase isn’t active in healthy adult tissues, so telomeres degrade and shorten as we age. When they get too short, the body knows to remove those damaged or dead cells.

In most cancers, telomerase is reactivated and telomeres are maintained, thus preserving the genetic material, and these are the cells that mutate and become immortal.

Telomerase is present in most cancer types, and it’s an attractive therapeutic target for cancer. However, scientists haven’t had much luck inhibiting telomerase activity in cancer, Ludlow said.

Ludlow’s group wanted to try a new approach, so they screened lung cancer cell lines for splicing genes (genes that modify RNA) that might regulate telomerase in cancer, and identified NOVA1.

They found that reducing the NOVA1 gene reduced telomerase activity, which led to shorter telomeres, and cancer cells couldn’t survive and divide.

Researchers only looked at non-small cell lung cancers, and NOVA1 was present in about 70 percent of them.

“Non-small cell lung cancer is the most prevalent form of age-related cancer, and 80 to 85 percent of all lung cancers are non-small cell,” Ludlow said. “But there really aren’t that many treatments for it.”

According to the American Cancer Society, lung cancer causes the most cancer deaths among men and women, and is the second most common cancer, aside from skin cancer.

Before researchers can target NOVA1 or telomerase splicing as a serious potential therapy for non-small cell lung cancer, they must gain a much better understanding of how telomerase is regulated. This research is a step in that direction.

Ludlow’s group is also looking at ways to directly impact telomerase splicing, in addition to reducing NOVA1.

Explore further: Blocking two enzymes could make cancer cells mortal

More information: Andrew T. Ludlow et al, NOVA1 regulates hTERT splicing and cell growth in non-small cell lung cancer, Nature Communications (2018). DOI: 10.1038/s41467-018-05582-x

https://medicalxpress.com/news/2018-08-nova1-gene-tumor-growth-common.html

Researchers at Ludwing Maximilliams Universitat Muchen have for the first time mapped the distribution of magnetic particles in the human brain. The study reveals that the particles are primarily located in the cerebellum and the brainstem, which are the more ancient parts of the brain.

Many living organisms, such as migratory birds, are thought to possess a magnetotactic sense, which enables them to respond to the Earth’s magnetic field. Whether or not humans are capable of sensing magnetism is the subject of debate. However, several studies have already shown that one of the preconditions required for such a magnetic sensory system is indeed met: magnetic particles exist in the human brain. Now a team led by Stuart A. Gilder (a professor at LMU‘s Department of Earth and Environmental Sciences) and Christoph Schmitz (a professor at LMU’s Department of Neuroanatomy) has systematically mapped the distribution of magnetic particles in human post mortem brains. Their findings were published in the journal Scientific Reports (Nature Publishing Group)

In their study, the LMU researchers confirmed the presence of magnetic particles in human brains. The particles were found primarily in the cerebellum and the brainstem, and there was striking asymmetry in the distribution between the left and right hemispheres of the brain. “The human brain exploits asymmetries in sensory responses for spatial orientation, and also for sound-source localization,” Schmitz explains. The asymmetric distribution of the magnetic particles is therefore compatible with the idea that humans might have a magnetic sensor. But in all probability, this sensor is much too insensitive to serve any useful biological function, he adds. Furthermore, the chemical nature of the magnetic particles remains unknown. “We assume that they are all made of magnetite (Fe3O4), but it is not yet possible to be sure,” says Gilder.

The study was funded by the Volkswagen Foundation’s “Experiment!” program, which is designed specifically to get daring new research projects, whose ultimate outcome is uncertain, off the ground. This is in contrast to traditional NIH-style support, which largely supports research that has already been conducted and for which the outcome is almost certain. The data were obtained from seven human post mortem brains, which had been donated for use in medical research. In all, a total of 822 tissue samples were subjected to magnetometry. The measurements were performed under the supervision of Stuart Gilder in a magnetically shielded laboratory located in a forest 80 km from Munich which is largely free from pervasive magnetic pollution that is characteristic of urban settings nowadays.

In further experiments, the LMU team plans to characterize the properties of the magnetic particles found in human brains. In collaboration with Professor Patrick R. Hof (Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York), they also hope to perform analogous localization studies on far larger mammals – whales. These huge marine mammals are known to migrate between feeding and breeding grounds across great distances in the world’s oceans. “We want determine whether we can detect magnetic particles in the brains of whales, and if so whether they are also asymmetrically distributed“ says Schmitz. “It goes without saying that such studies will be carried out on animals that have died of natural causes.”

https://www.en.uni-muenchen.de/news/newsarchiv/2018/schmitz_magnetite.html

Distribution of magnetic remanence carriers in the human brain
Stuart A. Gilder, Michael Wack, Leon Kaub, Sophie C. Roud, Nikolai Petersen, Helmut Heinsen, Peter Hillenbrand, Stefan Milz & Christoph Schmitz
Scientific Reportsvolume 8, Article number: 11363 (2018)

by SUKANYA CHARUCHANDRA

Even when Parkinson’s patients don’t have mutations in a gene called LRRK2, more of the active enzyme the gene generates is present in their brains than in healthy brains, researchers reported last week (July 25) in Science Translational Medicine. The finding suggests that LRRK2 inhibitors could help to reduce harmful effects of the enzyme in the vast majority of Parkinson’s patients.

“This is the really interesting bit of data … the demonstration that when you look in the brains of individuals with idiopathic Parkinson’s [where the cause is unknown], that there’s evidence that LRRK2 is activated,” says Patrick Lewis, who studies Parkinson’s disease at University College London and the University of Reading in the UK. He has collaborated with one of the paper’s coauthors but was not involved in this study.

Ten percent of Parkinson’s cases have known genetic causes. Three percent of cases are due to a mutation in LRRK2, the gene encoding the LRRK2 enzyme. The enzyme is highly active in Parkinson’s patients with a mutated LRRK2 gene, and the increased enzyme activity has been linked to the development of the disease.

In the new study, Timothy Greenamyre, a professor of neurology at the University of Pittsburgh, and his team wanted to look at the level of active LRRK2 in patients without an LRRK2 mutation. “Because [LRRK2] is a low-abundance protein, people have had difficulty detecting it,” Greenamyre says. To spot active LRRK2, the researchers first developed two versions of an assay: the first detects the active enzyme and the second, the inactive enzyme. In the first detection method, researchers used two different antibodies, one that binds to a specific subunit that acts as a known indicator of the active enzyme and another that binds to a different proximal portion of it. When both antibodies bind successfully, their close contact generates a fluorescent signal—a sign of active LRRK2. The second method detects a protein known to regulate LRRK2 activity. Higher levels of this protein indicate lower levels of available active LRRK2.

The team used the assay on postmortem brain tissue from Parkinson’s disease patients and from healthy individuals. The researchers observed higher levels of the active LRRK2 enzyme in substantia nigra dopamine-producing neurons—the death of which indicate neurodegenerative disease—in the brain tissue of Parkinson’s patients’ with no mutation in the LRRK2 gene than in healthy brain tissue.

“We have been wondering for a very long time whether LRRK2 plays a role in sporadic Parkinson’s disease,” says Mark Cookson, who studies the neurodegenerative disorder in the National Institutes of Health’s Laboratory of Neurogenetics. He has collaborated with Greenamyre before but was not involved in this work. According to Cookson, this study provides “defensive evidence” of LRRK2’s role in the disease, even in patients without a mutation in the gene.

In the next set of experiments, Greenamyre and his colleagues wanted to see if active LRRK2 turned up in two rat models of Parkinson’s disease. In the first rodent model, the animals were given the toxin rotenone to induce symptoms of the disease. Even without a mutation in the LRRK2 gene, the rats had higher levels of active LRRK2 protein. In the rats’ brains, the active LRRK2 enzymes were linked with clumps of another protein, α-synuclein. The clumps eventually help form Lewy bodies, a characteristic feature of Parkinson’s brains. In the second rodent model, the researchers overexpressed wildtype α-synuclein in the rats’ substantia nigra, which caused levels of active LRRK2 to rise. When the group treated the rotenone-rodent model with a drug that inhibited the LRRK2 protein, the number of clumps and Lewy bodies dropped.

The team also observed higher levels of reactive oxygen species (ROS)—chemically responsive molecules such as peroxides—in the brains of both rat models of Parkinson’s disease. As a result, Greenamyre and his colleagues wanted to see if directly increasing ROS led to more active LRRK2. In a third set of experiments, the team dosed healthy human cell lines with hydrogen peroxide and found the addition of the ROS increased the levels of LRRK2. A spike in ROS levels, the researchers suggest, activates LRRK2, which in turn aids in the development of some classic Parkinson’s features. Blocking the production of ROS resulted in a drop in active LRRK2. The result gives clues to an environmental cause for Parkinson’s disease.

Pharmaceutical companies are already developing LRRK2 inhibitors that can help the small percentage of Parkinson’s patients that have a mutation in the LRRK2 gene. “The inhibitors may benefit patients not only with the mutation but also patients who have idiopathic diseases—they’re much more common,” says coauthor Dario Alessi, a professor who studies signaling pathways in neurodegenerative disorders at the University of Dundee in the UK.

LRRK2 inhibitors, the researchers note, cause mild, yet reversible side effects, in the lungs and kidneys.

R.D. Maio et al., “LRRK2 activation in idiopathic Parkinson’s disease,” Science Translational Medicine, doi:10.1126/scitranslmed.aar5429, 2018.

https://www.the-scientist.com/news-opinion/key-enzyme-active-in-brains-of-patients-without-parkinsons-mutation-64599