Neuroscience

Articles and news from the latest research reports.

Posts tagged science

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Researchers generate new neurons in brains, spinal cords of living adult mammals UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells. Although the research indicates it may someday be possible to regenerate neurons from the body’s own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer’s disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research. Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells. Scientists in UT Southwestern’s Department of Molecular Biology first successfully turned astrocytes – the most common non-neuronal brain cells – into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology. “Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons,” said Dr. Chun-Li Zhang, assistant professor of molecular biology at UT Southwestern and senior author of both studies. “Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration,” Dr. Zhang explained. “Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming.” The scientists’ two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said. In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said. The current study reports neurogenesis (neuron creation) occurred in the spinal cords of both adult and aged (over one-year old) mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation. Neuroblasts took four weeks to form and eight weeks to mature into neurons, slower than neurogenesis reported in lab dish experiments, so researchers plan to conduct experiments to determine if the slower pace helps the newly generated neurons properly integrate into their environment. In the spinal cord study, SOX2-induced mature neurons created from reprogramming of astrocytes persisted for 210 days after the start of the experiment, the longest time the researchers examined, he added. Because tumor growth is a concern when cells are reprogrammed to an earlier stage of development, the researchers followed the mice in the Nature Cell Biology study for nearly a year to look for signs of tumor formation and reported finding none. (Image: Shutterstock)

Researchers generate new neurons in brains, spinal cords of living adult mammals

UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Although the research indicates it may someday be possible to regenerate neurons from the body’s own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer’s disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.

Spinal cord injuries can lead to an irreversible loss of neurons, and along with scarring, can ultimately lead to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can be an avenue to repair damage, but adult spinal cords have limited ability to produce new neurons. Biomedical scientists have transplanted stem cells to replace neurons, but have faced other hurdles, underscoring the need for new methods of replenishing lost cells.

Scientists in UT Southwestern’s Department of Molecular Biology first successfully turned astrocytes – the most common non-neuronal brain cells – into neurons that formed networks in mice. They now successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. The latest findings are published today in Nature Communications and follow previous findings published in Nature Cell Biology.

“Our earlier work was the first to clearly show in vivo (in a living animal) that mature astrocytes can be reprogrammed to become functional neurons without the need of cell transplantation. The current study did something similar in the spine, turning scar-forming astrocytes into progenitor cells called neuroblasts that regenerated into neurons,” said Dr. Chun-Li Zhang, assistant professor of molecular biology at UT Southwestern and senior author of both studies.

“Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration,” Dr. Zhang explained. “Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming.”

The scientists’ two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.

In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation (differentiation) into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.

The current study reports neurogenesis (neuron creation) occurred in the spinal cords of both adult and aged (over one-year old) mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation. Neuroblasts took four weeks to form and eight weeks to mature into neurons, slower than neurogenesis reported in lab dish experiments, so researchers plan to conduct experiments to determine if the slower pace helps the newly generated neurons properly integrate into their environment.

In the spinal cord study, SOX2-induced mature neurons created from reprogramming of astrocytes persisted for 210 days after the start of the experiment, the longest time the researchers examined, he added.

Because tumor growth is a concern when cells are reprogrammed to an earlier stage of development, the researchers followed the mice in the Nature Cell Biology study for nearly a year to look for signs of tumor formation and reported finding none.

(Image: Shutterstock)

Filed under valproic acid spinal cord astrocytes neurons neurodegeneration genetics neuroscience science

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New risk gene illuminates Alzheimer’s disease

A team of international scientists, including a researcher from Simon Fraser University, has isolated a gene thought to play a causal role in the development of Alzheimer’s disease. The Proceedings of the National Academy of Sciences recently published the team’s study.

The newly identified gene affects accumulation of amyloid-beta, a protein believed to be one of the main causes of the damage that underpins this brain disease in humans.

The gene encodes a protein that is important for intracellular transportation. Each brain cell relies on an internal highway system that transports molecular signals needed for the development, communication, and survival of the cell. 

This system’s impairment can disrupt amyloid-beta processing, causing its eventual accumulation. This contributes to the development of amyloid plaques, which are a key hallmark of Alzheimer’s disease.

Teasing out contributing disease factors, whether genetic or environmental, has long posed a challenge for Alzheimer’s researchers.

“Alzheimer’s is a multifactorial disease where a build-up of subtle problems develop in the nervous system over a span of decades,” says Michael Silverman, an SFU biology associate professor. He worked on the study with a team of Japanese scientists led by Dr. Takashi Morihara at Osaka University.   

Identifying these subtle, yet perhaps critical genetic contributions is challenging. “Alzheimer’s, like many human disorders, has a genetic component, yet many environmental and lifestyle factors contribute to the disease as well,” says Silverman. “In a sense, it is like looking for a needle in a complex genetic haystack.”

Only a small fraction of cases have a strong hereditary component, for example early-onset Alzheimer’s.

This breakthrough in Alzheimer’s research could open new avenues for the design of therapeutics and pave the way for early detection by helping healthcare professionals identify those who are predisposed to the disease.

“One possibility is that a genetic test for a particular variant of this newly discovered gene, along with other variants of genes that contribute to Alzheimer’s, will help to give a person their overall risk for the disease.  

“Lifestyle changes, such as improved diet, exercise, and an increase in cognitive stimulation may then help to slow the progression of Alzheimer’s,” says Silverman.

(Source: sfu.ca)

Filed under alzheimer's disease neurodegenerative diseases genetics neurons neuroscience science

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An Amazing Village Designed Just For People With Dementia Centuries after Shakespeare wrote about King Lear’s symptoms, there’s still no perfect way to care for sufferers of dementia and Alzheimer’s. In the Netherlands, however, a radical idea is being tested: Self-contained “villages” where people with dementia shop, cook, and live together—safely. We, as a population, are aging rapidly. According to the Alzheimer’s Association, one in three seniors today dies with dementia. The process of finding—and paying for—long-term care can be very confusing, unfortunately, and difficult for both loved ones and patients. Most caretakers are underpaid, overworked, and must drive far distances to their jobs—giving away some 17 billion unpaid hours of care a year. And it’s just going to get worse: Alzheimer’s has increased by an incredible 68 percent since 2000, and the cost of caring for sufferers will increase from $203 billion last year to $1.2 trillion by 2050. In short, we’re not prepared for the future that awaits us—financially, infrastructurally, or even socially. But in the small town of Weesp, in Holland—that bastion of social progressivism—at a dementia-focused living center called De Hogeweyk, aka Dementiavillage, the relationship between patients and their care is serving as a model for the rest of the world. Read more

An Amazing Village Designed Just For People With Dementia

Centuries after Shakespeare wrote about King Lear’s symptoms, there’s still no perfect way to care for sufferers of dementia and Alzheimer’s. In the Netherlands, however, a radical idea is being tested: Self-contained “villages” where people with dementia shop, cook, and live together—safely.

We, as a population, are aging rapidly. According to the Alzheimer’s Association, one in three seniors today dies with dementia. The process of finding—and paying for—long-term care can be very confusing, unfortunately, and difficult for both loved ones and patients. Most caretakers are underpaid, overworked, and must drive far distances to their jobs—giving away some 17 billion unpaid hours of care a year. And it’s just going to get worse: Alzheimer’s has increased by an incredible 68 percent since 2000, and the cost of caring for sufferers will increase from $203 billion last year to $1.2 trillion by 2050.

In short, we’re not prepared for the future that awaits us—financially, infrastructurally, or even socially. But in the small town of Weesp, in Holland—that bastion of social progressivism—at a dementia-focused living center called De Hogeweyk, aka Dementiavillage, the relationship between patients and their care is serving as a model for the rest of the world.

Read more

Filed under alzheimer's disease dementia dementia village de hogeweyk psychology neuroscience science

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New ideas change your brain cells A new University of British Columbia study identifies an important molecular change that occurs in the brain when we learn and remember. Published this month in Nature Neuroscience, the research shows that learning stimulates our brain cells in a manner that causes a small fatty acid to attach to delta-catenin, a protein in the brain. This biochemical modification is essential in producing the changes in brain cell connectivity associated with learning, the study finds. In animal models, the scientists found almost twice the amount of modified delta-catenin in the brain after learning about new environments. While delta-catenin has previously been linked to learning, this study is the first to describe the protein’s role in the molecular mechanism behind memory formation. “More work is needed, but this discovery gives us a much better understanding of the tools our brains use to learn and remember, and provides insight into how these processes become disrupted in neurological diseases,” says co-author Shernaz Bamji, an associate professor in UBC’s Life Sciences Institute. It may also provide an explanation for some mental disabilities, the researchers say. People born without the gene have a severe form of mental retardation called Cri-du-chat syndrome, a rare genetic disorder named for the high-pitched cat-like cry of affected infants. Disruption of the delta-catenin gene has also been observed in some patients with schizophrenia. “Brain activity can change both the structure of this protein, as well as its function,” says Stefano Brigidi, first author of the article and a PhD candidate Bamji’s laboratory. “When we introduced a mutation that blocked the biochemical modification that occurs in healthy subjects, we abolished the structural changes in brain’s cells that are known to be important for memory formation.” Background According to the researchers, more work is needed to fully establish the importance of delta-catenin in building the brain connectivity behind learning and memory. Disruptions to these nerve cell connections are also believed to cause neurodegenerative diseases such as Alzheimer’s and Huntington disease. Understanding the biochemical processes that are important for maintaining these connections may help address the abnormalities in nerve cells that occur in these disease states. (Image: Shutterstock)

New ideas change your brain cells

A new University of British Columbia study identifies an important molecular change that occurs in the brain when we learn and remember.

Published this month in Nature Neuroscience, the research shows that learning stimulates our brain cells in a manner that causes a small fatty acid to attach to delta-catenin, a protein in the brain. This biochemical modification is essential in producing the changes in brain cell connectivity associated with learning, the study finds.

In animal models, the scientists found almost twice the amount of modified delta-catenin in the brain after learning about new environments. While delta-catenin has previously been linked to learning, this study is the first to describe the protein’s role in the molecular mechanism behind memory formation.

“More work is needed, but this discovery gives us a much better understanding of the tools our brains use to learn and remember, and provides insight into how these processes become disrupted in neurological diseases,” says co-author Shernaz Bamji, an associate professor in UBC’s Life Sciences Institute.

It may also provide an explanation for some mental disabilities, the researchers say. People born without the gene have a severe form of mental retardation called Cri-du-chat syndrome, a rare genetic disorder named for the high-pitched cat-like cry of affected infants. Disruption of the delta-catenin gene has also been observed in some patients with schizophrenia.

“Brain activity can change both the structure of this protein, as well as its function,” says Stefano Brigidi, first author of the article and a PhD candidate Bamji’s laboratory. “When we introduced a mutation that blocked the biochemical modification that occurs in healthy subjects, we abolished the structural changes in brain’s cells that are known to be important for memory formation.”

Background

According to the researchers, more work is needed to fully establish the importance of delta-catenin in building the brain connectivity behind learning and memory. Disruptions to these nerve cell connections are also believed to cause neurodegenerative diseases such as Alzheimer’s and Huntington disease. Understanding the biochemical processes that are important for maintaining these connections may help address the abnormalities in nerve cells that occur in these disease states.

(Image: Shutterstock)

Filed under delta-catenin synaptic plasticity learning memory synapses genetic disorders neuroscience science

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Watching how the brain works

University of Miami researchers develop a method to visualize protein interactions in a living organism’s brain

There are more than a trillion cells called neurons that form a labyrinth of connections in our brains. Each of these neurons contains millions of proteins that perform different functions. Exactly how individual proteins interact to form the complex networks of the brain still remains as a mystery that is just beginning to unravel.

For the first time, a group of scientists has been able to observe intact interactions between proteins, directly in the brain of a live animal. The new live imaging approach was developed by a team of researchers at the University of Miami (UM).

image

(Image caption: Photonic resonance energy transfer described by Förster, or FRET, occurs when two small proteins come within a very small distance of each other — eight nanometers or less. The fluorescence lifetime of the donor molecule will become shorter — from 3 nanosecond to, perhaps, 2.5 nanoseconds. We then interpret this as evidence that the two proteins of interest are physically interacting with each other — a molecular signaling event. Credit: Akira Chiba/University of Miami)

"Our ultimate goal is to create the systematic survey of protein interactions in the brain," says Akira Chiba, professor of Biology in the College of Arts and Sciences at UM and lead investigator of the project. "Now that the genome project is complete, the next step is to understand what the proteins coded by our genes do in our body."

The new technique will allow scientists to visualize the interactions of proteins in the brain of an animal, along different points throughout its development, explains Chiba, who likens protein interactions to the way organisms associate with each other.

"We know that proteins are one billionth of a human in size. Nevertheless, proteins make networks and interact with each other, like social networking humans do," Chiba says. "The scale is very different, but it’s the same behavior happening among the basic units of a given network."

The researchers chose embryos of the fruit fly (Drosophila melanogaster) as an ideal model for the study. Because of its compact and transparent body, it is possible to visualize processes inside the Drosophila cells using a fluorescence lifetime imaging microscope (FLIM). The results of the observations are applicable to other animal brains, including the human brain.

The Drosophila embryos in the study contained a pair of fluorescent labeled proteins: a developmentally essential and ubiquitously present protein called Rho GTPase Cdc42 (cell division control protein 42), labeled with green fluorescent tag and its alleged signaling partner, the regulatory protein WASp (Wiskot-Aldrich Syndrome protein), labeled with red fluorescent tag. Together, these specialized proteins are believed to help neurons grow during brain development. The proteins were selected because the same (homolog) proteins exist in the human brain as well.

Previous methods required chemical or physical treatments that most likely disturb or even kill the cells. That made it impossible to study the protein interactions in their natural environment.

image

(Image caption: FRET (Förster resonance energy transfer) between the two interacting protein partners occurs, Cdc42 and WASp, within neurons, during the time and space that coincides with the formation of new synapses in the brain of the baby insect. Synapses connect individual neurons in the brain. Credit: Akira Chiba / University of Miami)

The current study addresses these challenges by using the occurrence of a phenomenon called Förster resonance energy transfer, or FRET. It occurs when two small proteins come within a very small distance of each other, (eight nanometers). The event is interpreted as the time and place where the particular protein interaction occurs within the living animal.

image

(Image caption: Proteins are one billionth of a human in size. Nevertheless, proteins make networks and interact with each other, like social networking humans do,” says Akira Chiba, professor of Biology in the College of Arts and Sciences at the University of Miami. “The scale is very different, but it’s the same behavior happening among the basic units of a given network.” Credit: Akira Chiba / University of Miami)

The findings show that FRET between the two interacting protein partners occurs within neurons, during the time and space that coincides with the formation of new synapses in the brain of the baby insect. Synapses connect individual neurons in the brain.

"Previous studies have demonstrated that Cdc42 and WASp can directly bind to each other in a test-tube, but this is the first direct demonstration that these two proteins are interacting within the brain," Chiba says.

(Source: eurekalert.org)

Filed under proteins protein interactions neurons CNS fruit flies FLIM FRET neuroscience science

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Researchers Pinpoint Brain Region Essential for Social Memory Columbia University Medical Center (CUMC) researchers have determined that a small region of the hippocampus known as CA2 is essential for social memory, the ability of an animal to recognize another of the same species. A better grasp of the function of CA2 could prove useful in understanding and treating disorders characterized by altered social behaviors, such as autism, schizophrenia, and bipolar disorder. The findings, made in mice, were published on Feb. 23, 2014, in the online edition of Nature. Scientists have long understood that the hippocampus—a pair of seahorse-shaped structures in the brain’s temporal lobes—plays a critical role in our ability to remember the who, what, where, and when of our daily lives. Recent studies have shown that different subregions of the hippocampus have different functions. For instance, the dentate gyrus is critical for distinguishing between similar environments, while CA3 enables us to recall a memory from partial cues (e.g., Proust’s famous madeleine). The CA1 region is critical for all forms of memory. “However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained largely unknown,” said senior author Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator. A few studies have suggested that CA2 might be involved in social memory, as this region has a high level of expression of a receptor for vasopressin, a hormone linked to sexual motivation, bonding, and other social behaviors. To learn more about this part of the hippocampus, the researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals. Once the neurons were inhibited, the mice were given a series of behavioral tests. “The mice looked quite normal until we looked at social memory,” said first author Frederick L. Hitti, an MD-PhD student in Dr. Siegelbaum’s laboratory, who developed the transgenic mouse. “Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.” In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice did not have a global lack of interest in novelty. In another experiment, the researchers tested whether the animals’ inability to form social memories might have to do with deficits in olfaction (sense of smell), which is crucial for normal social interaction. However, the mice showed no loss in ability to discriminate social or non-social odors. In humans, the importance of the hippocampus for social memory was famously illustrated by the case of Henry Molaison, who had much of his hippocampus removed by surgeons in 1953 in an attempt to cure severe epilepsy. Molaison (often referred to as HM in the scientific literature) was subsequently unable to form new memories of people. Scientists have observed that lesions limited to the hippocampus also impair social memory in both rodents and humans. “Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes,” said Dr. Siegelbaum. This possibility is supported by findings of a decreased number of CA2 inhibitory neurons in individuals with schizophrenia and bipolar disorder and altered vasopressin signaling in autism. Thus, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.
Researchers Pinpoint Brain Region Essential for Social Memory

Columbia University Medical Center (CUMC) researchers have determined that a small region of the hippocampus known as CA2 is essential for social memory, the ability of an animal to recognize another of the same species. A better grasp of the function of CA2 could prove useful in understanding and treating disorders characterized by altered social behaviors, such as autism, schizophrenia, and bipolar disorder. The findings, made in mice, were published on Feb. 23, 2014, in the online edition of Nature.

Scientists have long understood that the hippocampus—a pair of seahorse-shaped structures in the brain’s temporal lobes—plays a critical role in our ability to remember the who, what, where, and when of our daily lives. Recent studies have shown that different subregions of the hippocampus have different functions. For instance, the dentate gyrus is critical for distinguishing between similar environments, while CA3 enables us to recall a memory from partial cues (e.g., Proust’s famous madeleine). The CA1 region is critical for all forms of memory.

“However, the role of CA2, a relatively small region of the hippocampus sandwiched between CA3 and CA1, has remained largely unknown,” said senior author Steven A. Siegelbaum, PhD, professor of neuroscience and pharmacology, chair of the Department of Neuroscience, a member of the Mortimer B. Zuckerman Mind Brain Behavior Institute and Kavli Institute for Brain Science, and a Howard Hughes Medical Institute Investigator. A few studies have suggested that CA2 might be involved in social memory, as this region has a high level of expression of a receptor for vasopressin, a hormone linked to sexual motivation, bonding, and other social behaviors.

To learn more about this part of the hippocampus, the researchers created a transgenic mouse in which CA2 neurons could be selectively inhibited in adult animals. Once the neurons were inhibited, the mice were given a series of behavioral tests. “The mice looked quite normal until we looked at social memory,” said first author Frederick L. Hitti, an MD-PhD student in Dr. Siegelbaum’s laboratory, who developed the transgenic mouse. “Normally, mice are naturally curious about a mouse they’ve never met; they spend more time investigating an unfamiliar mouse than a familiar one. In our experiment, however, mice with an inactivated CA2 region showed no preference for a novel mouse versus a previously encountered mouse, indicating a lack of social memory.”

In two separate novel-object recognition tests, the CA2-deficient mice showed a normal preference for an object they had not previously encountered, showing that the mice did not have a global lack of interest in novelty. In another experiment, the researchers tested whether the animals’ inability to form social memories might have to do with deficits in olfaction (sense of smell), which is crucial for normal social interaction. However, the mice showed no loss in ability to discriminate social or non-social odors.

In humans, the importance of the hippocampus for social memory was famously illustrated by the case of Henry Molaison, who had much of his hippocampus removed by surgeons in 1953 in an attempt to cure severe epilepsy. Molaison (often referred to as HM in the scientific literature) was subsequently unable to form new memories of people. Scientists have observed that lesions limited to the hippocampus also impair social memory in both rodents and humans.

“Because several neuropsychiatric disorders are associated with altered social behaviors, our findings raise the possibility that CA2 dysfunction may contribute to these behavioral changes,” said Dr. Siegelbaum. This possibility is supported by findings of a decreased number of CA2 inhibitory neurons in individuals with schizophrenia and bipolar disorder and altered vasopressin signaling in autism. Thus, CA2 may provide a new target for therapeutic approaches to the treatment of social disorders.

Filed under hippocampus social memory schizophrenia autism social interaction dentate gyrus psychology neuroscience science

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New study settles how social understanding is performed by the brain A new study settles an important question about how social understanding is performed in the brain. The findings may help us to attain a better understanding of why people with autism and schizophrenia have difficulties with social interaction. In a study to be published in Psychological Science, researchers from Aarhus University and the University of Copenhagen demonstrate that brain cells in what is called the mirror system help people make sense of the actions they see other people perform in everyday life. Using magnetic stimulation to temporarily disrupt normal processing of the areas of the human brain involved in the production of actions of human participants, it is demonstrated that these areas are also involved in the understanding of actions. The study is the first to demonstrate a clear causal effect, whereas earlier studies primarily have looked at correlations, which are difficult to interpret. One of the researchers, John Michael, explains the process: “There has been a great deal of hype about the mirror system, and now we have performed an experiment that finally provides clear and straightforward evidence that the mirror system serves to help people make sense of others’ actions,” says John Michael. Understanding autism and schizophrenia The study shows that there are areas of the brain that are involved in the production of actions. And the researchers found evidence that these areas contribute to understanding others’ actions. This means that the same areas are involved in producing actions and understanding others’ actions. This helps us in everyday life, but it also holds great potential when trying to understand why people with autism and schizophrenia have difficulties with social interaction. “Attaining knowledge of the processes underlying social understanding in people in general is an important part of the process of attaining knowledge of the underlying causes of the difficulties that some people diagnosed with autism and schizophrenia experience in sustaining social understanding. But it is important to emphasise that this is just one piece of the puzzle.” “The findings may be interesting to therapists and psychiatrists who work with patients with schizophrenia or autism, or even to educational researchers,” adds John Michael. Facts about the empirical basis The participants (20 adults) came to the lab three times. They were given brain scans on the first visit. On the second and third, they received stimulation to their motor system and then performed a typical psychological task in which they watched brief videos of actors pantomiming actions (about 250 videos each time). After each video they had to choose a picture of an object that matched the pantomimed video. For example, a hammer was the correct answer for the video of an actor pretending to hammer. This task was intended to gauge their understanding of the observed actions. The researchers found that the stimulation interfered with their performance of this task. Innovative method The researchers used an innovative technique for magnetically stimulating highly specific brain areas in order to temporarily disrupt normal processing in those areas. The reason for using this technique (called continuous theta-burst stimulation) in general is that it makes it possible to determine which brain areas perform which functions. For example, if you stimulate (and thus temporarily impair) area A, and the participants subsequently have difficulty with some specific task (task T), then you can infer that area A usually performs task T. The effect goes away after 20 minutes, so this is a harmless and widely applicable way to identify which tasks are performed by which areas. With continuous theta-burst stimulation, you can actually determine that the activation of A contributes as a cause to people performing T. This method thus promises to be of great use to neuroscientists in the coming years.

New study settles how social understanding is performed by the brain

A new study settles an important question about how social understanding is performed in the brain. The findings may help us to attain a better understanding of why people with autism and schizophrenia have difficulties with social interaction.

In a study to be published in Psychological Science, researchers from Aarhus University and the University of Copenhagen demonstrate that brain cells in what is called the mirror system help people make sense of the actions they see other people perform in everyday life.

Using magnetic stimulation to temporarily disrupt normal processing of the areas of the human brain involved in the production of actions of human participants, it is demonstrated that these areas are also involved in the understanding of actions. The study is the first to demonstrate a clear causal effect, whereas earlier studies primarily have looked at correlations, which are difficult to interpret.

One of the researchers, John Michael, explains the process:

“There has been a great deal of hype about the mirror system, and now we have performed an experiment that finally provides clear and straightforward evidence that the mirror system serves to help people make sense of others’ actions,” says John Michael.

Understanding autism and schizophrenia

The study shows that there are areas of the brain that are involved in the production of actions. And the researchers found evidence that these areas contribute to understanding others’ actions. This means that the same areas are involved in producing actions and understanding others’ actions. This helps us in everyday life, but it also holds great potential when trying to understand why people with autism and schizophrenia have difficulties with social interaction.

“Attaining knowledge of the processes underlying social understanding in people in general is an important part of the process of attaining knowledge of the underlying causes of the difficulties that some people diagnosed with autism and schizophrenia experience in sustaining social understanding. But it is important to emphasise that this is just one piece of the puzzle.”

“The findings may be interesting to therapists and psychiatrists who work with patients with schizophrenia or autism, or even to educational researchers,” adds John Michael.

Facts about the empirical basis

The participants (20 adults) came to the lab three times. They were given brain scans on the first visit. On the second and third, they received stimulation to their motor system and then performed a typical psychological task in which they watched brief videos of actors pantomiming actions (about 250 videos each time). After each video they had to choose a picture of an object that matched the pantomimed video. For example, a hammer was the correct answer for the video of an actor pretending to hammer. This task was intended to gauge their understanding of the observed actions. The researchers found that the stimulation interfered with their performance of this task.

Innovative method

The researchers used an innovative technique for magnetically stimulating highly specific brain areas in order to temporarily disrupt normal processing in those areas. The reason for using this technique (called continuous theta-burst stimulation) in general is that it makes it possible to determine which brain areas perform which functions. For example, if you stimulate (and thus temporarily impair) area A, and the participants subsequently have difficulty with some specific task (task T), then you can infer that area A usually performs task T. The effect goes away after 20 minutes, so this is a harmless and widely applicable way to identify which tasks are performed by which areas.

With continuous theta-burst stimulation, you can actually determine that the activation of A contributes as a cause to people performing T. This method thus promises to be of great use to neuroscientists in the coming years.

Filed under social interaction autism schizophrenia mirror-neuron system theory of mind social cognition psychology neuroscience science

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Family problems experienced in childhood and adolescence affect brain development New research has revealed that exposure to common family problems during childhood and early adolescence affects brain development, which could lead to mental health issues in later life. The study led by Dr Nicholas Walsh, lecturer in developmental psychology at the University of East Anglia, used brain imaging technology to scan teenagers aged 17-19. It found that those who experienced mild to moderate family difficulties between birth and 11 years of age had developed a smaller cerebellum, an area of the brain associated with skill learning, stress regulation and sensory-motor control. The researchers also suggest that a smaller cerebellum may be a risk indicator of psychiatric disease later in life, as it is consistently found to be smaller in virtually all psychiatric illnesses. Previous studies have focused on the effects of severe neglect, abuse and maltreatment in childhood on brain development. However the aim of this research was to determine the impact, in currently healthy teenagers, of exposure to more common but relatively chronic forms of ‘family-focused’ problems. These could include significant arguments or tension between parents, lack of affection or communication between family members, physical or emotional abuse, and events which had a practical impact on daily family life and might have resulted in health, housing or school problems. Dr Walsh, from UEA’s School of Psychology, said: “These findings are important because exposure to adversities in childhood and adolescence is the biggest risk factor for later psychiatric disease. Also, psychiatric illnesses are a huge public health problem and the biggest cause of disability in the world. “We show that exposure in childhood and early adolescence to even mild to moderate family difficulties, not just severe forms of abuse, neglect and maltreatment, may affect the developing adolescent brain. We also argue that a smaller cerebellum may be an indicator of mental health issues later on. Reducing exposure to adverse social environments during early life may enhance typical brain development and reduce subsequent mental health risks in adult life.” The study, which was conducted with the University of Cambridge and the Medical Research Council Cognition and Brain Sciences Unit, Cambridge, is published in the journal NeuroImage: Clinical. The 58 teenagers who took part in the brain scanning were drawn from a larger study of 1200 young people, whose parents were asked to recall any negative life events their children had experienced between birth and 11 years of age. The interviews took place when the children were aged 14 and of the 58, 27 were classified as having been exposed to childhood adversities. At ages 14 and 17 the teenagers themselves also reported any negative events and difficulties they, their family or closest friends had experienced during the previous 12 months. A “significant and unexpected” finding was that the participants who reported stressful experiences when aged 14 were subsequently found to have increased volume in more regions of the brain when they were scanned aged 17-19. Dr Walsh said this could mean that mild stress occurring later in development may ‘inoculate’ teenagers, enabling them to cope better with exposure to difficulties in later life, and that it is the severity and timing of the experiences that may be important. “This study helps us understand the mechanisms in the brain by which exposure to problems in early-life leads to later psychiatric issues,” said Dr Walsh. “It not only advances our understanding of how the general psychosocial environment affects brain development, but also suggests links between specific regions of the brain and individual psychosocial factors. We know that psychiatric risk factors do not occur in isolation but rather cluster together, and using a new technique we show how the general clustering of adversities affects brain development.” The researchers also found at that those who had experienced family problems were more likely to have had a diagnosed psychiatric illness, have a parent with a mental health disorder and have negative perceptions of their how their family functioned.

Family problems experienced in childhood and adolescence affect brain development

New research has revealed that exposure to common family problems during childhood and early adolescence affects brain development, which could lead to mental health issues in later life.

The study led by Dr Nicholas Walsh, lecturer in developmental psychology at the University of East Anglia, used brain imaging technology to scan teenagers aged 17-19. It found that those who experienced mild to moderate family difficulties between birth and 11 years of age had developed a smaller cerebellum, an area of the brain associated with skill learning, stress regulation and sensory-motor control. The researchers also suggest that a smaller cerebellum may be a risk indicator of psychiatric disease later in life, as it is consistently found to be smaller in virtually all psychiatric illnesses.

Previous studies have focused on the effects of severe neglect, abuse and maltreatment in childhood on brain development. However the aim of this research was to determine the impact, in currently healthy teenagers, of exposure to more common but relatively chronic forms of ‘family-focused’ problems. These could include significant arguments or tension between parents, lack of affection or communication between family members, physical or emotional abuse, and events which had a practical impact on daily family life and might have resulted in health, housing or school problems.

Dr Walsh, from UEA’s School of Psychology, said: “These findings are important because exposure to adversities in childhood and adolescence is the biggest risk factor for later psychiatric disease. Also, psychiatric illnesses are a huge public health problem and the biggest cause of disability in the world.

“We show that exposure in childhood and early adolescence to even mild to moderate family difficulties, not just severe forms of abuse, neglect and maltreatment, may affect the developing adolescent brain. We also argue that a smaller cerebellum may be an indicator of mental health issues later on. Reducing exposure to adverse social environments during early life may enhance typical brain development and reduce subsequent mental health risks in adult life.”

The study, which was conducted with the University of Cambridge and the Medical Research Council Cognition and Brain Sciences Unit, Cambridge, is published in the journal NeuroImage: Clinical.

The 58 teenagers who took part in the brain scanning were drawn from a larger study of 1200 young people, whose parents were asked to recall any negative life events their children had experienced between birth and 11 years of age. The interviews took place when the children were aged 14 and of the 58, 27 were classified as having been exposed to childhood adversities. At ages 14 and 17 the teenagers themselves also reported any negative events and difficulties they, their family or closest friends had experienced during the previous 12 months.

A “significant and unexpected” finding was that the participants who reported stressful experiences when aged 14 were subsequently found to have increased volume in more regions of the brain when they were scanned aged 17-19. Dr Walsh said this could mean that mild stress occurring later in development may ‘inoculate’ teenagers, enabling them to cope better with exposure to difficulties in later life, and that it is the severity and timing of the experiences that may be important.

“This study helps us understand the mechanisms in the brain by which exposure to problems in early-life leads to later psychiatric issues,” said Dr Walsh. “It not only advances our understanding of how the general psychosocial environment affects brain development, but also suggests links between specific regions of the brain and individual psychosocial factors. We know that psychiatric risk factors do not occur in isolation but rather cluster together, and using a new technique we show how the general clustering of adversities affects brain development.”

The researchers also found at that those who had experienced family problems were more likely to have had a diagnosed psychiatric illness, have a parent with a mental health disorder and have negative perceptions of their how their family functioned.

Filed under brain development gray matter childhood adversity cerebellum psychology neuroscience science

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Study in Fruitflies Strengthens Connection Among Protein Misfolding, Sleep Loss, and Age

Pulling an “all-nighter” before a big test is practically a rite of passage in college. Usually, it’s no problem: You stay up all night, take the test, and then crash, rapidly catching up on lost sleep. But as we age, sleep patterns change, and our ability to recoup lost sleep diminishes.

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Researchers at the Perelman School of Medicine, University of Pennsylvania, have been studying the molecular mechanisms underpinning sleep. Now they report that the pathways of aging and sleep intersect at the circuitry of a cellular stress response pathway, and that by tinkering with those connections, it may be possible to alter sleep patterns in the aged for the better – at least in fruit flies.

Nirinjini Naidoo, PhD, associate professor in the Center for Sleep and Circadian Neurobiology and the Division of Sleep Medicine, led the study with postdoctoral fellow Marishka Brown, PhD, which was published online before print in the journal Neurobiology of Aging.

Increasing age is well known to disrupt sleep patterns in all sorts of ways. Elderly people sleep at night less than their younger counterparts and also sleep less well. Older individuals also tend to nap more during the day. Naidoo’s lab previously reported that aging is associated with increasing levels of protein unfolding, a hallmark of cellular stress called the “unfolded protein response.”

Protein misfolding is also a characteristic of several age-related neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, and as it turns out, also associated with sleep deprivation. Naidoo and her team wanted to know if rescuing proper protein folding behavior might counter some of the detrimental sleep patterns in elderly individuals.

Using a video monitoring system to compare the sleep habits of “young” (9–12 days old) and “aged” (8 weeks old) fruit flies, they found that aged flies took longer to recover from sleep deprivation, slept less overall, and had their sleep more frequently interrupted compared to younger control animals. However, adding a molecule that promotes proper protein folding – a molecular “chaperone” called PBA — mitigated many of those effects, effectively giving the flies a more youthful sleep pattern. PBA (sodium 4-phenylbutyrate) is a compound currently used to treat such protein-misfolding-based diseases as Parkinson’s and cystic fibrosis.

The team also asked the converse question: Can protein misfolding induce altered sleep patterns in young animals. Another drug, tunicamycin, induces protein misfolding and stress, and when the team fed it to young flies, their sleep patterns shifted towards those of aged flies, with less sleep overall, more interrupted sleep at night, and longer recovery from sleep deprivation.

Molecular analysis of sleep-deprived and PBA-treated flies suggested that PBA acts through the unfolded protein response. PBA, Naidoo says, had two effects on aged flies: it “consolidated” baseline sleep, increasing the total amount of time slept and shifted recovery sleep, after sleep deprivation, to look more like that of a young fly.

“It rescued the sleep patterns in the older flies,” she explains.

These results, Naidoo says, suggest three key messages. First, sleep loss leads to protein misfolding and cellular stress, and as we age, our ability to recover from that stress decreases. Second, aging and sleep apparently form a kind of negative “chicken-and-egg” feedback loop, in which sleep loss or sleep fragmentation lead to cellular stress, followed by neuronal dysfunction, and finally even poorer-quality sleep.

Sleep recharges neuronal batteries, Naidoo explains, and if a person is forced to stay awake, those batteries run down. Dwindling physiological resources must be devoted to the most critical cell functions, which do not necessarily include protein homeostasis. “Staying awake has a cost, and one of those costs is problems with protein folding.”

Finally, and most importantly, she says these results suggest — assuming they can be replicated in mice and humans – that it may be possible using drugs such as PBA to “fix sleep” in aged or mutant animals.

“People know that sleep deteriorates with aging,” Naidoo says, “But this might be able to be stopped or reversed with molecular chaperones.” Her team is now looking to determine if a similar situation exists in mammals and if better sleep translates into longer lifespan.

(Source: uphs.upenn.edu)

Filed under aging neurodegeneration sleep sleep deprivation proteins neuroscience science

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Study in Mice Raises Question: Could PTSD Involve Immune Cell Response to Stress?

Chronic stress that produces inflammation and anxiety in mice appears to prime their immune systems for a prolonged fight, causing the animals to have an excessive reaction to a single acute stressor weeks later, new research suggests.

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After the mice recovered from the effects of chronic stress, a single stressful event 24 days later quickly returned them to a chronically stressed state in biological and behavioral terms. Mice that had not experienced the chronic stress were unaffected by the single acute stressor.

The study further showed that immune cells called to action as a result of chronic stress ended up on standby in the animals’ spleens and were launched from that organ to respond to the later stressor.

Mice without spleens did not experience the same reactivation with the second stressor, signifying the spleen’s role as a reservoir for primed immune cells to remain until they’re activated in response to another stressor.

The excessive immune response and anxiety initiated by a brief stressor mimic symptoms of post-traumatic stress disorder.

The Ohio State University scientists are cautious about extending their findings to humans. But they say their decade of work with this model of stress suggests that the immune system has a significant role in affecting behavior. And they are the first to study this re-establishment of anxiety in animals with a later acute stressor.

“No one else has done a study of this length to see what happens to recovered animals if we subject them again to stress,” said Jonathan Godbout, a lead author of the study and associate professor of neuroscience at Ohio State. “That retriggering is a component of post-traumatic stress. The previously stressed mice are living a normal rodent life, and then this acute stress brings everything back. Animals that have never been exposed to stress before were unaffected by that one event – it didn’t change behavioral or physiological properties.”

The research is published online in the journal Biological Psychiatry.

(Source: researchnews.osu.edu)

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Filed under PTSD chronic stress anxiety immune system neuroscience science

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