Neuroscience

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Posts tagged blood cells

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New blood cells fight brain inflammation

Hyperactivity of our immune system can cause a state of chronic inflammation. If chronic, the inflammation will affect our body and result in disease. In the devastating disease multiple sclerosis, hyperactivity of immune cells called T-cells induce chronic inflammation and degeneration of the brain. Researchers at BRIC, the University of Copenhagen, have identified a new type of regulatory blood cells that can combat such hyperactive T-cells in blood from patients with multiple sclerosis. By stimulating the regulatory blood cells, the researchers significantly decreased the level of brain inflammation and disease in a biological model. The results are published in the journal Nature Medicine.

Molecule activate anti-inflammatory blood cells

The new blood cells belong to the group of our white blood cells called lymphocytes. The cells express a molecule called FoxA1 that the researchers found is responsible for the cells’ development and suppressive functions.

"We knew that some unidentified blood cells were able to inhibit multiple sclerosis-like disease in mice and through gene analysis we found out, that these cells are a subset of our lymphocytes expressing the gene FoxA1. Importantly, when inserting FoxA1 into normal lymphocytes with gene therapy, we could change them to actively regulate inflammation and inhibit multiple sclerosis", explains associated professor Yawei Liu leading the experimental studies.

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Image caption: Tissue sections from an untreated diseased brain and a FoxA1-treated brain from the researchers biological model. (Photo: Yawei Liu)

Activating own blood cells for treatment of disease

FoxA1 expressing lymphocytes were not known until now, and this is the first documentation of their importance in controlling multiple sclerosis. The number of people living with this devastating disease around the world has increased by 10 percent in the past five years to 2.3 million. It affects women twice more than men and no curing treatment exists. The research group headed by professor Shohreh Issazadeh-Navikas from BRIC examined blood of patients with multiple sclerosis, before and after two years of treatment with the drug interferon-beta. They found that patients who benefit from the treatment increase the number of this new blood cell type, which fight disease.

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Image caption: FoxA1-lymphocytes. (Photo: Yawei Liu)

“From a therapeutic viewpoint, our findings are really interesting and we hope that they can help finding new treatment options for patients not benefiting from existing drugs, especially more chronic and progressive multiple sclerosis patients. In our model, we could activate lymphocytes by chemical stimulation and gene therapy, and we are curios whether this can be a new treatment strategy”, says professor Shohreh Issazadeh-Navikas.

And this is exactly what the research group will focus on at next stage of their research. They have already started to test whether the new FoxA1-lymphocytes can prevent degradation of the nerve cell’s myelin layer and brain degeneration in a model of progressive multiple sclerosis. Besides multiple sclerosis, knowledge on how to prevent chronic inflammation will also be valuable for other autoimmune diseases like type 1 diabetes, inflammatory bowel disease and rheumatoid arthritis, where inflammation is a major cause of the disease.

(Source: news.ku.dk)

Filed under brain inflammation blood cells lymphocytes FoxA1 MS neurodegeneration medicine science

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PTSD research: distinct gene activity patterns from childhood abuse

Abuse during childhood is different.

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A study of adult civilians with PTSD (post-traumatic stress disorder) has shown that individuals with a history of childhood abuse have distinct, profound changes in gene activity patterns, compared to adults with PTSD but without a history of child abuse.

A team of researchers from Atlanta and Munich probed blood samples from 169 participants in the Grady Trauma Project, a study of more than 5000 Atlanta residents with high levels of exposure to violence, physical and sexual abuse and with high risk for civilian PTSD.

The results were published Monday, April 29 in Proceedings of the National Academy of Sciences, Early Edition.

“These are some of the most robust findings to date showing that different biological pathways may describe different subtypes of a psychiatric disorder, which appear similar at the level of symptoms but may be very different at the level of underlying biology,” says Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences at Emory University School of Medicine and Yerkes National Primate Research Center.

“As these pathways become better understood, we expect that distinctly different biological treatments would be implicated for therapy and recovery from PTSD based on the presence or absence of past child abuse.”

Ressler, a Howard Hughes Medical Institute Investigator, is co-director of the Grady Trauma Project, along with co-author Bekh Bradley, PhD, assistant professor of psychiatry and behavioral sciences at Emory and director of the Trauma Recovery Program at the Atlanta Veterans Affairs Medical Center.

The first author of the paper is Divya Mehta, PhD, a postdoctoral fellow in Munich. The senior author is Elisabeth Binder, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory and group leader at the Max-Planck Institute of Psychiatry in Munich, Germany.

Mehta and her colleagues examined changes in the patterns of which genes were turned on and off in blood cells from patients. They also looked at patterns of methylation, a DNA modification on top of the four letters of the genetic code that causes genes to be ‘silenced’ or made inactive.

Study participants were divided into three groups: people who experienced trauma without developing PTSD, people with PTSD who were exposed to child abuse, and people with PTSD who were not exposed to child abuse.

The researchers were surprised to find that although hundreds of genes had significant changes in activity in the PTSD with and without child abuse groups, there was very little overlap in patterns between these groups. The two groups shared similar symptoms of PTSD, which include intrusive thoughts such as nightmares and flashbacks, avoidance of trauma reminders, and symptoms of hyperarousal and hypervigilance.

The PTSD with child abuse group displayed more changes in genes linked with development of the nervous system and regulation of the immune system, while the PTSD minus child abuse group displayed more changes in genes linked with apoptosis (cell death) and growth rate regulation. In addition, changes in methylation were more frequent in the PTSD with child abuse group. The authors believe that these biological pathways may lead to different mechanisms of PTSD symptom formation within the brain.

The Max Planck/Emory scientists were probing gene activity in blood cells, rather than brain tissue. Similar results have been obtained by researchers studying the influence of child abuse on the brains of people who had committed suicide.

“Traumatic events that happen in childhood are embedded in the cells for a long time,” Binder says. “Not only the disease itself, but the individual’s life experience is important in the biology of PTSD, and this should be to be reflected in the way we treat these disorders.”

(Source: news.emory.edu)

Filed under child abuse PTSD gene activity dna methylation blood cells psychology neuroscience science

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Blood Clots Are Ready for Their Close-Up


A blood clot is one of the final steps in a complex process with which the human body seals a rupture in an injured blood vessel. Clotting involves interactions between millions of blood cells, microscopic cell fragments called platelets, and various proteins. First, platelets rush to the site of injury and join together with an inner layer of fibrin and collagen proteins to form a sticky web around the break. Red blood cells are then trapped in the web, forming a clot. In certain cases a clot can block arteries and vessels that feed the brain or heart, impeding blood flow and eventually contributing to a stroke or heart attack.
Creating accurate, real-time computer simulations of how blood clots work—and the role they play in medical emergencies—could, in the future, dramatically improve the way that doctors predict the risk of damaging clots and treat the damage incurred by strokes and heart attacks. The models could, for example, help doctors position a stent—a tube placed in a blood vessel to help keep it open—before a risky surgery or offer a new way to test the effects of drugs on the circulatory system. In order to be truly accurate and useful, however, such simulations would have to account for billions of tiny cellular machines, all moving through the blood—something that has never been comprehensively modeled before.


View a slide show of blood-clot formation visualization

Blood Clots Are Ready for Their Close-Up

A blood clot is one of the final steps in a complex process with which the human body seals a rupture in an injured blood vessel. Clotting involves interactions between millions of blood cells, microscopic cell fragments called platelets, and various proteins. First, platelets rush to the site of injury and join together with an inner layer of fibrin and collagen proteins to form a sticky web around the break. Red blood cells are then trapped in the web, forming a clot. In certain cases a clot can block arteries and vessels that feed the brain or heart, impeding blood flow and eventually contributing to a stroke or heart attack.

Creating accurate, real-time computer simulations of how blood clots work—and the role they play in medical emergencies—could, in the future, dramatically improve the way that doctors predict the risk of damaging clots and treat the damage incurred by strokes and heart attacks. The models could, for example, help doctors position a stent—a tube placed in a blood vessel to help keep it open—before a risky surgery or offer a new way to test the effects of drugs on the circulatory system. In order to be truly accurate and useful, however, such simulations would have to account for billions of tiny cellular machines, all moving through the blood—something that has never been comprehensively modeled before.

View a slide show of blood-clot formation visualization

Filed under arteries blood cells blood clots brain stroke neuroscience science

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Unique Genetic Marker Discovery May Help Predict Multiple Sclerosis Relapse

Scientists may be one step closer to predicting the uncertain course of relapsing-remitting multiple sclerosis (MS), a disease that can lay dormant for months or years, thanks to the discovery of a unique genetic marker. The marker, detailed by researchers in the August edition of The Journal of Immunology, is the first of its kind to be directly linked to MS.

The study, supported by funding from both the National Institutes of Health (NIH) and the Ohio State Center for Clinical and Translational Science (CCTS) was conducted by a team of scientists with The Ohio State University using blood samples from patients with MS, as well as mouse models. Researchers uncovered the molecule miR-29, while working to identify a biomarker in the blood that could indicate if a patient had an ongoing inflammatory response, such as MS.

“Our research was inspired by the knowledge gap that existed between microRNA and MS, as well as the unpredictable nature of MS,” said Kristen Smith, Ph.D., principal investigator, who received a “mentorship grant” to conduct the study alongside senior scientists at The Ohio State University Wexner Medical Center. “By identifying a unique marker associated with MS, we hope to inspire a relatively noninvasive test that could identify and predict the course of the disease, helping clinicians tailor therapies to disease progression.”

Source: newswise

Filed under MS biomarker blood cells immune system miR-29 neuroscience brain science

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The adult human circulatory system contains between 20 and 30 trillion red blood cells (RBCs), the precise size and number of which can vary from person to person. Some people may have fewer, but larger RBCs, while others may have a larger number of smaller RBCs. Although these differences in size and number may seem inconsequential, they raise an important question: Just what controls these characteristics of RBCs?
By analyzing the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells, researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs. Their findings are reported in the September 14 issue of Genes and Development.

The adult human circulatory system contains between 20 and 30 trillion red blood cells (RBCs), the precise size and number of which can vary from person to person. Some people may have fewer, but larger RBCs, while others may have a larger number of smaller RBCs. Although these differences in size and number may seem inconsequential, they raise an important question: Just what controls these characteristics of RBCs?

By analyzing the results of genome-wide association studies (GWAS) in conjunction with experiments on mouse and human red blood cells, researchers in the lab of Whitehead Institute Founding Member Harvey Lodish have identified the protein cyclin D3 as regulating the number of cell divisions RBC progenitors undergo, which ultimately affects the resulting size and quantity of RBCs. Their findings are reported in the September 14 issue of Genes and Development.

Filed under RBCs GWAS genomics science neuroscience blood cells genetics cell division cyclin D3

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Study uses stem cells to boost red blood cell production

August 7, 2012

(HealthDay) — Using human stem cells, scientists have developed methods to boost the production of red blood cells, according to a new study.

Their discovery could significantly increase the blood supply needed for blood transfusions, the researchers said, and their methods can be used to produce any blood type.

"Being able to produce red blood cells from stem cells has the potential to overcome many difficulties of the current system, including sporadic shortages," Dr. Anthony Atala, editor of the journal Stem Cells Translational Medicine, in which the study appeared, said in a journal news release.

"This team has made a significant contribution to scientists’ quest to produce red blood cells in the lab," said Atala, who is also director of the Wake Forest Institute for Regenerative Medicine.

How does the new process work?

"We combined different cell-expansion protocols into a ‘cocktail’ that increased the number of cells we could produce by 10- to 100-fold," said researcher Eric Bouhassira, of the Albert Einstein College of Medicine in New York City.

Currently, the blood needed for life-saving transfusions is obtained only through donations. As a result, blood can be in short supply, particularly for those with rare blood types. The researchers produced a higher yield of red blood cells by using stem cells from cord blood and circulating blood as well as embryonic stem cells, according to the release.

"The ability of scientists to grow large quantities of red blood cells at an industrial scale could revolutionize the field of transfusion medicine," Bouhassira said. "Collecting blood through a donation-based system is serving us well but it is expensive, vulnerable to disruption and insufficient to meet the needs of some people who need ongoing transfusions. This could be a viable long-term alternative."

Source: medicalxpress.com

Filed under science neuroscience brain psychology blood cells stem cells

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Neurons derived from cord blood cells may represent new therapeutic option

July 16, 2012

For more than 20 years, doctors have been using cells from blood that remains in the placenta and umbilical cord after childbirth to treat a variety of illnesses, from cancer and immune disorders to blood and metabolic diseases.

This microscope image shows a colony of neurons derived from cord-blood cells using stem cell reprogramming technology. The green and red glow indicates that the cells are producing protein makers found in neurons, evidence that the cord-blood cells did in fact morph into neurons. The blue glow marks the nuclei of the neurons. Credit: Image: Courtesy of Alessandra Giorgetti

Now, scientists at the Salk Institute for Biological Studies have found a new way-using a single protein, known as a transcription factor-to convert cord blood (CB) cells into neuron-like cells that may prove valuable for the treatment of a wide range of neurological conditions, including stroke, traumatic brain injury and spinal cord injury.

The researchers demonstrated that these CB cells, which come from the mesoderm, the middle layer of embryonic germ cells, can be switched to ectodermal cells, outer layer cells from which brain, spinal and nerve cells arise. “This study shows for the first time the direct conversion of a pure population of human cord blood cells into cells of neuronal lineage by the forced expression of a single transcription factor,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, who led the research team. The study, a collaboration with Fred H. Gage, a professor in Salk’s Laboratory of Genetics, and his team, was published on July 16 in the Proceedings of the National Academy of Sciences.

"Unlike previous studies, where multiple transcription factors were necessary to convert skin cells into neurons, our method requires only one transcription factor to convert CB cells into functional neurons," says Gage.

The Salk researchers used a retrovirus to introduce Sox2, a transcription factor that acts as a switch in neuronal development, into CB cells. After culturing them in the laboratory, they discovered colonies of cells expressing neuronal markers. Using a variety of tests, they determined that the new cells, called induced neuronal-like cells (iNC), could transmit electrical impulses, signaling that the cells were mature and functional neurons. Additionally, they transferred the Sox2-infused CB cells to a mouse brain and found that they integrated into the existing mouse neuronal network and were capable of transmitting electrical signals like mature functional neurons.

"We also show that the CB-derived neuronal cells can be expanded under certain conditions and still retain the ability to differentiate into more mature neurons both in the lab and in a mouse brain," says Mo Li, a scientist in Belmonte’s lab and a co-first author on the paper with Alessandra Giorgetti, of the Center for Regenerative Medicine, in Barcelona, and Carol Marchetto of Gage’s lab. "Although the cells we developed were not for a specific lineage-for example, motor neurons or mid-brain neurons-we hope to generate clinically relevant neuronal subtypes in the future."

Importantly, says Marchetto, “We could use these cells in the future for modeling neurological diseases such as autism, schizophrenia, Parkinson’s or Alzheimer’s disease.”

Cord blood cells, says Giorgetti, offer a number of advantages over other types of stem cells. First, they are not embryonic stem cells and thus they are not controversial. They are more plastic, or flexible, than adult stem cells from sources like bone marrow, which may make them easier to convert into specific cell lineages. The collection of CB cells is safe and painless and poses no risk to the donor, and they can be stored in blood banks for later use.

"If our protocol is developed into a clinical application, it could aid in future cell-replacement therapies," says Li. "You could search all the cord blood banks in the country to look for a suitable match."

Provided by Salk Institute

Source: medicalxpress.com

Filed under science neuroscience brain psychology neuron blood cells disorder disease

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