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News Article | May 9, 2017
Site: www.eurekalert.org

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.


News Article | May 9, 2017
Site: www.chromatographytechniques.com

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.


News Article | May 11, 2017
Site: www.eurekalert.org

New research in The FASEB Journal suggests that the protein Efr3a regulates the BDNF-TrkB signaling pathway, which plays an important role in regulating learning and memory New research published online in The FASEB Journal sheds important light on the inner workings of learning and memory. Specifically, scientists show that a plasma membrane protein, called Efr3, regulates brain-derived neurotrophic factor-tropomyosin-related kinase B signaling pathway (BNDF-TrkB) and affects the generation of new neurons in the hippocampus of adult brains. In turn, this generation of new neurons plays a significant role in learning and memory. "Our study demonstrates that Efr3a is associated with BDNF signaling and adult neurogenesis, which are important for learning and memory," said Binggui Sun, Ph.D., a researcher involved in the work at the Department of Neurobiology, Key Laboratory of Medical Neurobiology (Ministry of Health of China), Key Laboratory of Neurobiology of Zhejiang Province, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. "We hope our results will provide new insights into the mechanisms underlying learning and memory." To draw their conclusions, Sun and colleagues bred Efr3af/f mice and then crossed these mice with another group to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. Brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology. Also, the BDNF-TrkB signaling pathway was enhanced in the hippocampus of Efr3a-deficient mice, as reflected by increased expression of BDNF-TrkB, and the downstream molecules, including phospho-MAPK (mitogen-activated protein kinase) and phospho-Akt. "This study once again emphasizes the extreme importance of neurogenesis specifically linked to neurotrophic signaling in the hippocampus." said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. "We are again reminded of how far we have come from the era in which neurogenesis in the adult mammalian brain was not believed to even occur." Submit to The FASEB Journal by visiting http://fasebj. , and receive monthly highlights by signing up at http://www. . The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the world's most cited biology journals according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century. FASEB is composed of 30 societies with more than 125,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy. Details: Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Luo, and Binggui Sun. Brain-specific ablation of Efr3a promotes adult hippocampal neurogenesis via the brain-derived neurotrophic factor pathway. FASEB J. doi:10.1096/fj.201601207R ; http://www.


News Article | May 9, 2017
Site: www.chromatographytechniques.com

Certain blood vessels in the brainstem constrict when blood vessels elsewhere in the body would dilate. And that contrary behavior is what keeps us breathing, according to a new paper by UConn researchers published May 8 in eLife. If the body were a marching band, the brainstem would be the drum major. It keeps our heart beating and our lungs breathing in the essential rhythms of life. And just like a drum major, the job is more complex than it looks. If cellular waste products build up in the body, the brainstem has to jolt the lungs into action without disrupting other bodily functions, as surely as a drum major reins in a wayward woodwind section without losing the low brass. Neuroscientists studying the brainstem have focused on neurons, which are brain cells that send signals to one another and all over the body. But focusing just on the neurons in the brainstem is like staring only at the drum major's hands. Recently, neuroscientists have come to understand that astrocytes, cells once thought to simply provide structure to the brain, also release signaling molecules that regulate neurons' function. But until now, no one even considered the possibility that blood vessels may be similarly specialized. For more than a century, doctors and scientists have known that blood vessels dilate when cellular waste products like carbon dioxide build up. Widening the vessels allows fresh blood to flush through, carrying in oxygen and washing away the acidic carbon dioxide. This has been shown to be true throughout the body, and is standard dogma in undergraduate physiology classes. UConn physiologist Dan Mulkey was teaching exactly that to undergraduates one day when he realized that it couldn't possibly be true in a certain part of the brainstem. "I thought, wow. If that happened in the region of the brain I study, it would be counterproductive," Mulkey says. He studies the retrotrapezoid nucleus (RTN), a small region in the brainstem that controls breathing. He's shown in the past that RTN neurons respond to rising levels of carbon dioxide in the bloodstream by stimulating the lungs to breathe. But if the blood vessels in the RTN dilated in response to rising carbon dioxide the same way blood vessels do everywhere else, it would wash out that all-important signal, preventing cells in the RTN from doing their job driving us to breathe. It would be as if the drum major didn't notice the percussion section wandering off to left field. When Mulkey returned to the lab, he asked his team, including NIH postdoctoral fellow Virginia Hawkins, to see how blood vessels in thin slices of brainstem respond to carbon dioxide. And they saw it was indeed true - RTN blood vessels constricted when carbon dioxide levels rose. But blood vessels from slices of cortex (the wrinkled top part of the brain) dilated in response to high carbon dioxide, just like the rest of the body. But how did the blood vessels know to act differently in the RTN? Mulkey guessed that RTN astrocytes had something to do with it. He suspected that the astrocytes were releasing adenosine triphosphate (ATP), a small molecule cells can use to signal one another. And that was causing the RTN blood vessels to constrict. When they tested it, they found the hypothesis was correct. The astrocytes in the RTN were behaving differently than astrocytes anywhere else in the body. When these brainstem astrocytes detected high levels of carbon dioxide, they released ATP signaling to the neurons and blood vessels. When the researchers induced the astrocytes artificially to release ATP, they got the same results. Bathing the RTN blood vessels directly in ATP also caused them to constrict. Blocking ATP receptors blocked the ability of blood vessels to respond to carbon dioxide. When the team did the same experiments in live animals, they got the same results. Perhaps most importantly, manipulating blood vessels in the RTN actually influenced how animals breathe, thus linking regulation of blood vessel diameter to behavior. The majority of this research was done by UConn undergraduates, including Ashley Trinh, Colin Cleary, and Todd Dubreuil, as well as Elliot Rodriguez, a summer student in the National Science Foundation (NSF) Research Experience for Undergraduates in Physiology and Neurobiology program at UConn, who studies at Gettysburg College in Pennsylvania the rest of the year. The students' work uncovered a major discovery in neurophysiology. The work was funded in part by grants from the National Institutes of Health (HL104101 HL126381) and the Connecticut Department of Public Health (150263). "This is a big change in how we think about breathing," Mulkey says. And about blood vessels. Even in a single organ like the brain, the purpose of blood flow is not the same everywhere. Tailored responses in the RTN keep the body's drum major conducting, and let the band play on.


University of Toronto and Baycrest Rotman Research Institute (RRI) scientists have discovered a potential brain imaging predictor for dementia, which illustrates that changes to the brain's structure may occur years prior to a diagnosis, even before individuals notice their own memory problems. The joint study, published in the Neurobiology of Aging on May 8, looked at older adults who are living in the Toronto community without assistance and who were unaware of any major memory problems, but scored below the normal benchmark on a dementia screening test. Within these older adults, researchers also found evidence of less brain tissue in the same subregion of the brain where Alzheimer's disease originates (the anterolateral entorhinal cortex located in the brain's temporal lobe). This U of T-Baycrest study is the first to measure this particular brain subregion in older adults who do not have a dementia diagnosis or memory problems that affect their day-to-day routine. It is also the first study to demonstrate that performance on the Montreal Cognitive Assessment (MoCA) dementia screening test is linked to the volume (size) of this subregion, along with other brain regions affected early in the course of Alzheimer's disease. "This work is an important first step in determining a procedure to identify older adults living independently at home without memory complaints who are at risk for dementia," says Dr. Morgan Barense of U of T's Department of Psychology and senior author on the study. The team studied 40 adults between the ages of 59 and 81 who live independently (or with a spouse) at home. All participants were tested on the MoCA. Those scoring below 26 - a score that indicates a potential problem in memory and thinking skills and suggests further dementia screening is needed - were compared to those scoring 26 and above. "The early detection of these at-risk individuals has the potential to facilitate drug developments or other therapeutic interventions for Alzheimer's disease," says Dr. Rosanna Olsen, first author on the study, RRI scientist and assistant professor in U of T's Department of Psychology. "This research also adds to our basic understanding of aging and the early mechanisms of Alzheimer's disease." Scientists were able to reliably measure the volume of the anterolateral entorhinal cortex by using high-resolution brain scans that were collected for each participant. The strongest volume differences were found in the exact regions of the brain in which Alzheimer's disease originates. The researchers are planning a follow-up study to determine whether the individuals who demonstrated poor thinking and memory abilities and smaller brain volumes indeed go on to develop dementia. "The MoCA is good at diagnosing mild cognitive impairment (MCI) (a condition that is likely to develop into Alzheimer's) and we are seeing that it may identify MCI in people who are not aware of a decline in their memory and thinking skills," said Dr. Barense. Alzheimer's disease is a devastating neurodegenerative illness with widespread personal, societal and economic consequences. Currently, 564,000 Canadians currently live with dementia and 1.1 million Canadians are affected by the disease, according to the Alzheimer Society of Canada. There are 25,000 new cases of dementia diagnosed every year in Canada and it costs $10.4 billion to care for those living with dementia. "A key take-away from the study is that it highlights the utility of the MoCA test in identifying individuals who are at-risk for dementia," said Dr. Olsen. Adults who are 40+ and interested in testing their memory and attention prior to raising concerns with their doctor can consult Baycrest's scientifically-validated, online brain health assessment tool, Cogniciti at http://www. . Research for this study was conducted with support from the Canadian Institutes of Health Research, the Canada Research Chairs program, the James S McDonnell Foundation, the Natural Sciences and Engineering Research Council, and an Early Researcher Award from the Ontario Government. The research team included RRI senior scientist Dr. Jennifer Ryan, former RRI post-doctoral fellow, Dr. Maria D'Angelo, and graduate students, Lok-Kin Yeung, Alix Noly-Gandon, and research assistants, Arber Kacollja and Victoria Smith. Established in 1827, the University of Toronto is Canada's largest university, recognized as a global leader in research and teaching. The university consistently ranks among the top 25 universities in the world. Its distinguished faculty, institutional record of ground-breaking scholarship and wealth of innovative academic opportunities continually attract outstanding academics and students from around the world. Baycrest Health Sciences is a global leader in geriatric residential living, healthcare, research, innovation and education, with a special focus on brain health and aging. Fully affiliated with the University of Toronto, Baycrest provides excellent care for older adults combined with an extensive clinical training program for the next generation of healthcare professionals and one of the world's top research institutes in cognitive neuroscience, the Rotman Research Institute. Baycrest is home to the federally and provincially-funded Canadian Centre for Aging and Brain Health Innovation, a solution accelerator focused on driving innovation in the aging and brain health sector, and is the developer of Cogniciti - a free online memory assessment for Canadians 40+ who are concerned about their memory. Founded in 1918 as the Jewish Home for Aged, Baycrest continues to embrace the long-standing tradition of all great Jewish healthcare institutions to improve the well-being of people in their local communities and around the globe. For more information please visit: http://www. The Rotman Research Institute at Baycrest Health Sciences is a premier international centre for the study of human brain function. Through generous support from private donors and funding agencies, the institute is helping to illuminate the causes of cognitive decline in seniors, identify promising approaches to treatment, and lifestyle practices that will protect brain health longer in the lifespan.


News Article | May 16, 2017
Site: www.sciencedaily.com

In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer's disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment. Already in a very early phase of Alzheimer's disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet's Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer's disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease. "There's been an international race to measure tau spread, and we probably got there first," says Professor Nordberg. "There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer's disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis." The study included 16 patients at different stages of Alzheimer's disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals. "We also saw a strong direct correlation between size of deposit and episodic memory impairment," continues Professor Nordberg. "This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn't seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism." The study was conducted in collaboration with Uppsala University, where the PET scans were performed.


News Article | May 16, 2017
Site: www.eurekalert.org

In a new study presented in Molecular Psychiatry, researchers at Karolinska Institutet have measured how deposits of the pathological protein tau spread through the brain over the course of Alzheimer's disease. Their results show that the size of the deposit and the speed of its spread differ from one individual to the next, and that large amounts of tau in the brain can be linked to episodic memory impairment. Already in a very early phase of Alzheimer's disease there is an accumulation of tau in the brain cells, where its adverse effect on cell function causes memory impairment. It is therefore an attractive target for vaccine researchers. For the present study, Professor Agneta Nordberg at Karolinska Institutet's Department of Neurobiology, Care Sciences and Society and her doctoral student Konstantinos Chiotis along with the rest of her team used PET brain imaging to measure the spread of tau deposits as well as the amyloid plaque associated with Alzheimer's disease, and charted the energy metabolism of the brain cells. They then examined how these three parameters changed over the course of the disease. "There's been an international race to measure tau spread, and we probably got there first," says Professor Nordberg. "There are no previous reports on how tau deposits spread after 17 months into the disease. Our results can improve understanding of tau accumulation in Alzheimer's disease, help ongoing research to quantify the effect of tau vaccines, and enable early diagnosis." The study included 16 patients at different stages of Alzheimer's disease from the memory unit at Karolinska Hospital in Huddinge. The patients were given a series of neurological memory tests and underwent PET scans at 17-month intervals. While all 16 participants had abundant amyloid plaque deposition in the brain, the size and speed of spread of their tau deposits differed significantly between individuals. "We also saw a strong direct correlation between size of deposit and episodic memory impairment," continues Professor Nordberg. "This could explain why the disease progresses at such a varying rate from one patient to the other. That said, tau doesn't seem to have much of an effect on the global general memory, which is more reasonably related to brain metabolism." The study was conducted in collaboration with Uppsala University, where the PET scans were performed. The study was financed by the Swedish Research Council, the Swedish Foundation for Strategic Research, Stockholm County Council (ALF funds), the Strategic Research Area in neuroscience at Karolinska Institutet, the Gamla Tjänarinnor Foundation, the Axel Linder Foundation, the Gun and Bertil Stohne Foundation, KI's Funds, the Swedish Brain Fund, the Swedish Alzheimer's Foundation, the Swedish Dementia Foundation, the Wenner-Gren Foundations, KTH - SCC research grants and the EU INMiND project. Publication: "Longitudinal changes of tau PET imaging in relation to hypometabolism in prodromal and Alzheimer's disease dementia", K Chiotis, L Saint-Aubert, E Rodriguez-Vieitez, A Leuzy, O Almkvist, I Savitcheva, M Jonasson, M Lubberink, A Wall, G Antoni och A Nordberg, Molecular Psychiatry, online 16 May 2017.


News Article | May 19, 2017
Site: www.sciencedaily.com

A research team from the University of Plymouth, University of Southampton and the Alexander Fleming Biomedical Sciences Research Center, Vari, Greece, have studied two structurally-similar proteins in the adult brain and have found that they play distinct roles in the development of dementia. Their study is published in the journal Neurobiology of Disease. The understanding and knowledge gained from this study could lead to effective therapies for dementia and other neurodegenerative diseases. Tau proteins stabilise microtubules in the brain and nervous system. Microtubules help form the structure of cells and other functions, such as providing the rail tracks for transport between cells. In the brain of dementia patients, the abnormal clumping of Tau proteins have long been linked to changes in nerve cell activation and ultimately cell death. Two structurally different forms of Tau exist. The research team expressed these two forms of human Tau in nerve cells of the Drosophila (fruit fly) brain, examining their effects on nerve cell survival and activation, fly movement and memory formation. The results show that these two proteins differ in terms of biology and pathological potential. One leads to poor communication between nerves associated with movement. The other leads to greater neurodegeneration and impairments in learning and memory. This is important because defects in the proteins have a bearing on neurodegenerative diseases such as dementia. Designing drugs which target each form specifically should help to improve specific symptoms. Involved in the study from the University of Plymouth is Dr Torsten Bossing. He commented: "With each new discovery like this we move one step closer to finding effective drug treatments for debilitating neurodegenerative diseases. This is an important study carried out using nerve cells from fruit flies and it has the potential over the coming years to be developed through more testing and clinical trials. We firmly believe that the answer to the question of how we treat conditions such as dementia lies at this cellular level."


News Article | May 19, 2017
Site: www.eurekalert.org

Discovery relating to brain proteins could lead to new effective therapies for dementia and other neurodegenerative diseases A research team from the University of Plymouth, University of Southampton and the Alexander Fleming Biomedical Sciences Research Center, Vari, Greece, have studied two structurally-similar proteins in the adult brain and have found that they play distinct roles in the development of dementia. Their study is published in the prestigious journal Neurobiology of Disease. The understanding and knowledge gained from this study could lead to effective therapies for dementia and other neurodegenerative diseases. Tau proteins stabilise microtubules in the brain and nervous system. Microtubules help form the structure of cells and other functions, such as providing the rail tracks for transport between cells. In the brain of dementia patients, the abnormal clumping of Tau proteins have long been linked to changes in nerve cell activation and ultimately cell death. Two structurally different forms of Tau exist. The research team expressed these two forms of human Tau in nerve cells of the Drosophila (fruit fly) brain, examining their effects on nerve cell survival and activation, fly movement and memory formation. The results show that these two proteins differ in terms of biology and pathological potential. One leads to poor communication between nerves associated with movement. The other leads to greater neurodegeneration and impairments in learning and memory. This is important because defects in the proteins have a bearing on neurodegenerative diseases such as dementia. Designing drugs which target each form specifically should help to improve specific symptoms. Involved in the study from the University of Plymouth is Dr Torsten Bossing. He commented: "With each new discovery like this we move one step closer to finding effective drug treatments for debilitating neurodegenerative diseases. This is an important study carried out using nerve cells from fruit flies and it has the potential over the coming years to be developed through more testing and clinical trials. We firmly believe that the answer to the question of how we treat conditions such as dementia lies at this cellular level." The study received funding from the Royal Society (Plymouth), the Wessex Medical Trust and Gerald Kerkut Trust (Southampton), and the European Social Fund and Greek National Funds (THALIS-UOA) (Vari).


News Article | April 25, 2017
Site: www.eurekalert.org

Irvine, Calif., April 24, 2017 -- Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease. The finding marks an important step in the use of induced pluripotent stem (iPS) cells for targeted approaches to better understand and potentially treat neurological diseases such as Alzheimer's. These iPS cells are derived from existing adult skin cells and show increasing utility as a promising approach for studying human disease and developing new therapies. Skin cells were donated from patients at the UCI Alzheimer's Disease Research Center. The study, led by Edsel Abud, Wayne Poon and Mathew Blurton Jones of UCI, used a genetic process to reprogram these cells into a pluripotent state capable of developing into any type of cell or tissue of the body. The researchers then guided these pluripotent cells to a new state by exposing the cells to a series of differentiation factors which mimicked the developmental origin of microglia. The resulting cells act very much like human microglial cells. Their study appears in the current issue of Neuron. In the brain, microglia mediate inflammation and the removal of dead cells and debris. These cells make up 10- to 15-percent of brain cells and are needed for the development and maintenance of neural networks. "Microglia play an important role in Alzheimer's and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimer's-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies," said Blurton-Jones, an assistant professor of the Department of Neurobiology & Behavior and Director of the ADRC iPS Core. "Scientists have had to rely on mouse microglia to study the immunology of AD. This discovery provides a powerful new approach to better model human disease and develop new therapies," added Poon, a UCI MIND associate researcher. Along those lines, the researchers examined the genetic and physical interactions between Alzheimer's disease pathology and iPS-microglia. They are now using these cells in three-dimensional brain models to understand how microglia interact with other brain cells and influence AD and the development of other neurological diseases. "Our findings provide a renewable and high-throughput method for understanding the role of inflammation in Alzheimer's disease using human cells," said Abud, an M.D./Ph.D. student. "These translational studies will better inform disease-modulating therapeutic strategies." Blurton Jones, Abud and Poon are with UCI's Institute for Memory Impairments and Neurological Disorders (UCI MIND). Ricardo Ramirez, Eric Martinez, Cecilia Nguyen, Sean Newman, Vanessa Scarfone, Samuel E. Marsh, Cristhian Fimbres, Chad A. Caraway, Ali Mortazavi, Michael Cahalan, Brian Cummings, Gianna Fote, Andriy Yeromin and Anshu Agrawal with UCI; Luke Healy and Jack Antel with McGill University, Montreal; Rakez Kayed with the University of Texas Medical Branch, Galveston, Texas; Karen Gylys with UCLA; and Abdullah Madany and Monica Carson with UC Riverside contributed to the study. The National Institutes of Health, the California Institute for Regenerative Medicine, and the Susan Scott Foundation provided support.

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