A team of researchers from the University of Aveiro and the University of Porto, both in Portugal, and the University of Birmingham in the U.K. has found that for humans, the brain and testis have the highest number of common proteins. In their paper published in the journal Royal Society Open Biology, the group describes their study of protein similarities between tissues.
In this new effort, the researchers noted that evidence from other studies has found some signs of similarities between testis and the human brain. Intrigued, they initiated a study that involved analyzing the proteins produced by different parts of the body and then comparing them to see similarities. The researchers found the greatest similarities between the brain and testicles—13,442 of them. This finding suggests that the brain and the testicles share the highest number of genes of any organs in the body.
The team next focused on the shared proteins and found that most of them were involved in the development of tissue and communications. They suggest this finding was not surprising, considering that proteins from both organs consume high amounts of fuel—one to process thinking, the other to produce millions of sperm every day. They also note that testis and nerve cells are both involved in moving material created inside of them to an outside environment—sperm cells move fertilization factors and neurons move neurotransmitters. Both are part of processes known as exocytosis. Additionally, as part of exocytosis, sperm allow parts of themselves to fuse with an egg. With neurons, exocytosis involves creating neurites that allow for communication between cells.
The researchers also took a step back from their work, noting that there may be a reason for the similarities between the proteins produced by the two organs. They note, for example, that prior research efforts have shown a link between brain disorders and sexual dysfunction. And some have even found a link between the quality of sperm produced and intelligence. They suggest more research is required to better understand the connections between the two organs, if there are any.
n a mouse model of stuttering (lower panel), there are fewer astrocytes, shown in green, compared to controls (upper panel) in the corpus callosum, the area of the brain that enables the left and right hemispheres to communicate.Tae-Un Han, Ph.D., NIDCD postdoctoral researcher
Researchers believe that stuttering — a potentially lifelong and debilitating speech disorder — stems from problems with the circuits in the brain that control speech, but precisely how and where these problems occur is unknown.
Using a mouse model of stuttering, scientists report that a loss of cells in the brain called astrocytes are associated with stuttering. The mice had been engineered with a human gene mutation previously linked to stuttering.
The study(link is external), which appeared online in the Proceedings of the National Academy of Sciences, offers insights into the neurological deficits associated with stuttering.
The loss of astrocytes, a supporting cell in the brain, was most prominent in the corpus callosum, a part of the brain that bridges the two hemispheres. Previous imaging studies have identified differences in the brains of people who stutter compared to those who do not. Furthermore, some of these studies in people have revealed structural and functional problems in the same brain region as the new mouse study.
The study was led by Dennis Drayna, Ph.D., of the Section on Genetics of Communication Disorders, at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health. Researchers at the Washington University School of Medicine in St. Louis and from NIH’s National Institute of Biomedical Imaging and Bioengineering, and National Institute of Mental Health collaborated on the research.
“The identification of genetic, molecular, and cellular changes that underlie stuttering has led us to understand persistent stuttering as a brain disorder,” said Andrew Griffith, M.D., Ph.D., NIDCD scientific director. “Perhaps even more importantly, pinpointing the brain region and cells that are involved opens opportunities for novel interventions for stuttering — and possibly other speech disorders.”
Stuttering is characterized by pauses and repeated or prolonged sounds, syllables or words, which disrupt the normal flow of speech. People who stutter know what they want to say, but they have trouble saying it. The condition is most commonly seen in young children who typically outgrow the problem. However, for 1 in 4 children who experience early stuttering, the condition persists as a lifelong communication problem. It is estimated that as many as 1% of adults in the United States are affected by stuttering.
“The brain imaging studies of people who stutter are important, but those results can only take us so far,” said Drayna. One challenge, he said, is that the imaging studies cannot decipher if the differences contribute to stuttering or are an effect of stuttering.
“By taking a genetic approach, we have been able to begin deciphering the neuropathology of stuttering, first at the molecular level by identifying genetic mutations, and now at the cellular level,” added Drayna.
Earlier research by Drayna and colleagues has identified several genes associated with stuttering. In this study, the researchers set out to identify changes in the brain brought on by the mutations in a gene called GNPTAB, one of the genes previously linked to stuttering. The scientists engineered this human stuttering mutation into the mice to create a mouse model. The mice with the GNPTAB mutation had long pauses in their stream of vocalizations, similar to those found in people with the same mutation. Like people who stutter, the mice were normal in all other ways, reinforcing earlier research that suggests that the mice can serve as a valid animal model for important features of this disorder.
The investigators next examined brain tissue from the mice and found a decrease in astrocytes, but not other cell types, in the animals with the genetic mutation compared to the mice without the mutation. Astrocytes play a critical role in supporting nerve cells by carrying out a wide range of functions, such as supplying nerve cells with oxygen and nutrients and providing structural support.
The loss of astrocytes was more pronounced in the corpus callosum of the mutant mice. In addition, using advanced magnetic resonance imaging (MRI) methods, the researchers detected reduced local volume of the corpus callosum in the mutant mice despite normal diffusion tensor MRI values, providing further support for a defect in this brain region.
Containing as many as 200 million nerve fibers, the corpus callosum enables communication between the brain’s left and right hemispheres, helping to integrate signals for processes that involve both hemispheres, such as physical coordination and use of language.
Follow-up experiments in which the GNPTAB human stuttering mutation was introduced into individual brain cell types — rather than the entire mouse — confirmed that the vocalization defect is specific to astrocytes. The mice did not have the stuttering-like vocalizations when the mutation was engineered into other types of brain cells.
All of the stuttering genes that have been identified over the past decade are involved in intracellular trafficking, the process that cells use to move proteins and other components to their correct locations within the cell. Defects in cellular trafficking have been linked to other neurological disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Alzheimer’s disease, suggesting that certain nerve cell pathways are particularly sensitive to impairment of this process. The research does not indicate, however, that persistent stuttering is an early indicator of these other disorders.
If future research confirms that stuttering in people with GNPTAB mutations derives from a loss of astrocytes in the brain, these findings could open the door to new therapeutic strategies for some people with persistent developmental stuttering by targeting associated molecular pathways and cells.
This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
This research was supported by the Intramural Research Program of NIH, NIDCD (Z1A-000046-18), the National Institute of Mental Health’s Rodent Behavioral Core, and the National Heart, Lung, and Blood Institute’s Animal MRI Core.
This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.
NIH study suggests our brains may use short rest periods to strengthen memories.
In a study of healthy volunteers, National Institutes of Health researchers found that our brains may solidify the memories of new skills we just practiced a few seconds earlier by taking a short rest. The results highlight the critically important role rest may play in learning.
In a study of healthy volunteers, NIH researchers found that taking short breaks, early and often, may help our brains learn new skills.Cohen lab, NIH/NINDS
“Everyone thinks you need to ‘practice, practice, practice’ when learning something new. Instead, we found that resting, early and often, may be just as critical to learning as practice,” said Leonardo G. Cohen, M.D., Ph.D., senior investigator at NIH’s National Institute of Neurological Disorders and Stroke and a senior author of the paper published in the journal Current Biology. “Our ultimate hope is that the results of our experiments will help patients recover from the paralyzing effects caused by strokes and other neurological injuries by informing the strategies they use to ‘relearn’ lost skills.”
The study was led by Marlene Bönstrup, M.D., a postdoctoral fellow in Dr. Cohen’s lab. Like many scientists, she held the general belief that our brains needed long periods of rest, such as a good night’s sleep, to strengthen the memories formed while practicing a newly learned skill. But after looking at brain waves recorded from healthy volunteers in learning and memory experiments at the NIH Clinical Center, she started to question the idea.
The waves were recorded from right-handed volunteers with a highly sensitive scanning technique called magnetoencephalography. The subjects sat in a chair facing a computer screen and under a long cone-shaped brain scanning cap. The experiment began when they were shown a series of numbers on a screen and asked to type the numbers as many times as possible with their left hands for 10 seconds; take a 10 second break; and then repeat this trial cycle of alternating practice and rest 35 more times. This strategy is typically used to reduce any complications that could arise from fatigue or other factors.
As expected, the volunteers’ speed at which they correctly typed the numbers improved dramatically during the first few trials and then leveled off around the 11th cycle. When Dr. Bönstrup looked at the volunteers’ brain waves she observed something interesting.
“I noticed that participants’ brain waves seemed to change much more during the rest periods than during the typing sessions,” said Dr. Bönstrup. “This gave me the idea to look much more closely for when learning was actually happening. Was it during practice or rest?”
By reanalyzing the data, she and her colleagues made two key findings. First, they found that the volunteers’ performance improved primarily during the short rests, and not during typing. The improvements made during the rest periods added up to the overall gains the volunteers made that day. Moreover, these gains were much greater than the ones seen after the volunteers returned the next day to try again, suggesting that the early breaks played as critical a role in learning as the practicing itself.
Second, by looking at the brain waves, Dr. Bönstrup found activity patterns that suggested the volunteers’ brains were consolidating, or solidifying, memories during the rest periods. Specifically, they found that the changes in the size of brain waves, called beta rhythms, correlated with the improvements the volunteers made during the rests.
Further analysis suggested that the changes in beta oscillations primarily happened in the right hemispheres of the volunteers’ brains and along neural networks connecting the frontal and parietal lobes that are known to help control the planning of movements. These changes only happened during the breaks and were the only brain wave patterns that correlated with performance.
“Our results suggest that it may be important to optimize the timing and configuration of rest intervals when implementing rehabilitative treatments in stroke patients or when learning to play the piano in normal volunteers,” said Dr. Cohen. “Whether these results apply to other forms of learning and memory formation remains an open question.”
Dr. Cohen’s team plans to explore, in greater detail, the role of these early resting periods in learning and memory.
Assessing the patterns of energy use and neuronal activity simultaneously in the human brain improves our understanding of how alcohol affects the brain, according to new research by scientists at the National Institutes of Health.
NIH scientists present a new method for combining measures of brain activity (left) and glucose consumption (right) to study regional specialization and to better understand the effects of alcohol on the human brain.Dr. Ehsan Shokri Kojori, NIAAA
The new approach for characterizing brain energetic patterns could also be useful for studying other neuropsychiatric diseases. A report of the findings is now online in Nature Communications.
“The brain uses a lot of energy compared to other body organs, and the association between brain activity and energy utilization is an important marker of brain health,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of NIH, which funded the study. “This study introduces a new way of characterizing how brain activity is related to its consumption of glucose, which could be very useful in understanding how the brain uses energy in health and disease.”
The research was led by Dr. Ehsan Shokri-Kojori and Dr. Nora D. Volkow of the NIAAA Laboratory of Neuroimaging. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH. In previous studies they and their colleagues have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, which is assessed through changes in blood oxygenation.
“The findings from this study highlight the relevance of energetics for ensuring normal brain function and reveal how it is disrupted by excessive alcohol consumption,” says Dr. Volkow.
In their new study, the researchers combined human brain imaging techniques for measuring glucose metabolism and neuronal activity to derive new measures, which they termed power and cost.
“We measured power by observing to what extent brain regions are active and use energy,” explained Dr. Shokri-Kojori. “We measured cost of brain regions by observing to what extent their energy use exceeds their underlying activity.”
In a group of healthy volunteers, the researchers showed that different brain regions that serve distinct functions have notably different power and different cost. They then investigated the effects of alcohol on these new measures by assessing a group of people that included light drinkers and heavy drinkers and found that both acute and chronic exposure to alcohol affected power and cost of brain regions.
“In heavy drinkers, we saw less regional power for example in the thalamus, the sensory gateway, and frontal cortex of the brain, which is important for decision making,” said Dr. Shokri-Kojori. “These decreases in power were interpreted to reflect toxic effects of long-term exposure to alcohol on the brain cells.”
The researchers also found a decrease in power during acute alcohol exposure in the visual regions, which was related to disruption of visual processing. At the same time, visual regions had the most significant decreases in cost of activity during alcohol intoxication, which is consistent with the reliance of these regions on alternative energy sources such as acetate, a byproduct of alcohol metabolism.
They conclude that despite widespread decreases in glucose metabolism in heavy drinkers compared to light drinkers, heavy drinking shifts the brain toward less efficient energetic states. Future studies are needed to investigate the mechanisms contributing to this relative inefficiency.
“Studying energetic signatures of brain regions in different neuropsychiatric diseases is an important future direction, as the measures of power and cost may provide new multimodal biomarkers for such disorders,” says Dr. Shokri-Kojori.
The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol use disorder. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at: https://www.niaaa.nih.gov.
NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.
NIH-funded study suggests immune cells rush through channels to get to injured tissue quickly.
Bone marrow, the spongy tissue inside most of our bones, produces red blood cells as well as immune cells that help fight off infections and heal injuries.
Unearthing Secret Tunnels Between the Skull and Brain – Neuroscience News
According to a new study of mice and humans, tiny tunnels run from skull bone marrow to the lining of the brain and may provide a direct route for immune cells responding to injuries caused by stroke and other brain disorders.
The study was funded in part by the National Institutes of Health and published in Nature Neuroscience.
“We always thought that immune cells from our arms and legs traveled via blood to damaged brain tissue. These findings suggest that immune cells may instead be taking a shortcut to rapidly arrive at areas of inflammation,” said Francesca Bosetti, Ph.D., program director at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which provided funding for the study. “Inflammation plays a critical role in many brain disorders and it is possible that the newly described channels may be important in a number of conditions. The discovery of these channels opens up many new avenues of research.”
Using state-of-the-art tools and cell-specific dyes in mice, Matthias Nahrendorf, M.D., Ph.D., professor at Harvard Medical School and Massachusetts General Hospital in Boston, and his colleagues were able to distinguish whether immune cells traveling to brain tissue damaged by stroke or meningitis, came from bone marrow in the skull or the tibia, a large legbone. In this study, the researchers focused on neutrophils, a particular type of immune cell, which are among the first to arrive at an injury site.
Results in mouse brains showed that during stroke, the skull is more likely to supply neutrophils to the injured tissue than the tibia. In contrast, following a heart attack, the skull and tibia provided similar numbers of neutrophils to the heart, which is far from both of those areas.
Dr. Nahrendorf’s group also observed that six hours after stroke, there were fewer neutrophils in the skull bone marrow than in the tibia bone marrow, suggesting that the skull marrow released many more cells to the injury site. These findings indicate that bone marrow throughout the body does not uniformly contribute immune cells to help injured or infected tissue and suggests that the injured brain and skull bone marrow may “communicate” in some way that results in a direct response from adjacent leukocytes.
Dr. Nahrendorf’s team found that differences in bone marrow activity during inflammation may be determined by stromal cell-derived factor-1 (SDF–1), a molecule that keeps immune cells in the bone marrow. When levels of SDF-1 decrease, neutrophils are released from marrow. The researchers observed levels of SDF-1 decreasing six hours after stroke, but only in the skull marrow, and not in the tibia. The results suggest that the decrease in levels of SDF-1 may be a response to local tissue damage and alert and mobilize only the bone marrow that is closest to the site of inflammation.
Next, Dr. Nahrendorf and his colleagues wanted to see how the neutrophils were arriving at the injured tissue.
“We started examining the skull very carefully, looking at it from all angles, trying to figure out how neutrophils are getting to the brain,” said Dr. Nahrendorf. “Unexpectedly, we discovered tiny channels that connected the marrow directly with the outer lining of the brain.”
With the help of advanced imaging techniques, the researchers watched neutrophils moving through the channels. Blood normally flowed through the channels from the skull’s interior to the bone marrow, but after a stroke, neutrophils were seen moving in the opposite direction to get to damaged tissue.
Dr. Nahrendorf’s team detected the channels throughout the skull as well as in the tibia, which led them to search for similar features in the human skull. Detailed imaging of human skull samples obtained from surgery uncovered the presence of the channels. The channels in the human skull were five times larger in diameter compared to those found in mice. In human and mouse skulls, the channels were found in the both in the inner and outer layers of bone.
Future research will seek to identify the other types of cells that travel through the newly discovered tunnels and the role these structures play in health and disease.
This study was supported by NINDS (NS084863) and the NIH’s National Heart, Lung and Blood Institute (HL139598).
The NINDS is the United States leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
The nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs
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