 |
|
UNC-Duke study: Impaired brain plasticity linked to Angelman syndrome learning deficits
May 11, 2009CHAPEL HILL -- How might disruption of a single gene in the brain cause the severe cognitive deficits associated with Angelman syndrome, a neurogenetic disorder? Researchers at the University of North Carolina at Chapel Hill School of Medicine and Duke University now believe they have the answer: impaired brain plasticity.
"When we have experiences, connections between brain cells are modified so that we can learn," said Benjamin Philpot, Ph.D., professor of cell and molecular physiology at UNC and senior author of the study published online May 10 in Nature Neuroscience. "By strengthening and weakening appropriate connections between brain cells, a process termed 'synaptic plasticity', we are able to constantly learn and adapt to an ever-changing environment."
Angelman syndrome occurs in one in 15,000 live births. The most common genetic defect of the syndrome is the lack of expression of the gene UBE3A on chromosome 15. The syndrome often is misdiagnosed as cerebral palsy or autism. Characteristics of the syndrome include intellectual and developmental delay, severe mental retardation lack of speech (minimal or no use of words), seizures, sleep disturbance, hand flapping and motor and balance disorders.
Philpot and his co-authors studied a mouse model of Angelman syndrome. In these mice, the gene UBE3A is functionally deficient. The study found that brain cells in the mice lacked the ability to appropriately strengthen or weaken their connections in the neocortex, a region of the brain that is important for cognitive abilities.
"If brain cells were unable to modify their connections with new experiences, then we would have difficulty learning," said Michael Ehlers, M.D., Ph.D., professor of neurobiology at Duke and co-senior author of the study. "We have found that a specific form of brain plasticity is severely impaired in a mouse model of Angelman syndrome and this prevents brain circuits from encoding information provided by sensory experiences. In addition, an exciting possibility is that the defect we have found may be a more general feature of other disorders of brain development including autism."
The inability of brain cells to encode information from experiences in the Angelman syndrome model suggests that this is the basis for the learning difficulties in these patients.
"It is difficult to study how experiences lead to changes in the brain in models of mental retardation," said Koji Yashiro, PhD, a former graduate student in Philpot's lab and lead author of the study, now a scientist with Urogenix, Inc. in Research Triangle Park, North Carolina. "Instead of studying a complex learning model, we studied how connections between brain cells change in visual areas of mice exposed to light or kept in darkness. This approach revealed that brain cells in normal mice can modify their connections in response to changes in visual experiences, while the brain cells in Angelman syndrome model mice could not."
An unexpected finding was that the plasticity of the cellular connections could be restored in visual areas of the brain after brief periods of visual deprivation. Philpot said the observation that the brain defect could be reversed "is very encouraging, as it suggests that viable behavioral or pharmacological therapies are likely to exist."
"By showing that brain plasticity can be restored in Angelman syndrome model mice, our findings suggest that brain cells in Angelman syndrome patients maintain a latent ability to express plasticity. We are now collaborating to find a way to tap into this latent plasticity, as this could offer a treatment, or even a cure, for Angelman syndrome," said Philpot.
Philpot added, "This same experimental approach could also reveal how brain cells encode information from experiences in other related disorders, such as autism, and may provide a model to find cures for a variety of neurodevelopmental disorders."
University of North Carolina School of Medicine
Philpot and his co-authors studied a mouse model of Angelman syndrome. In these mice, the gene UBE3A is functionally deficient. The study found that brain cells in the mice lacked the ability to appropriately strengthen or weaken their connections in the neocortex, a region of the brain that is important for cognitive abilities.
"If brain cells were unable to modify their connections with new experiences, then we would have difficulty learning," said Michael Ehlers, M.D., Ph.D., professor of neurobiology at Duke and co-senior author of the study. "We have found that a specific form of brain plasticity is severely impaired in a mouse model of Angelman syndrome and this prevents brain circuits from encoding information provided by sensory experiences. In addition, an exciting possibility is that the defect we have found may be a more general feature of other disorders of brain development including autism."
The inability of brain cells to encode information from experiences in the Angelman syndrome model suggests that this is the basis for the learning difficulties in these patients.
"It is difficult to study how experiences lead to changes in the brain in models of mental retardation," said Koji Yashiro, PhD, a former graduate student in Philpot's lab and lead author of the study, now a scientist with Urogenix, Inc. in Research Triangle Park, North Carolina. "Instead of studying a complex learning model, we studied how connections between brain cells change in visual areas of mice exposed to light or kept in darkness. This approach revealed that brain cells in normal mice can modify their connections in response to changes in visual experiences, while the brain cells in Angelman syndrome model mice could not."
An unexpected finding was that the plasticity of the cellular connections could be restored in visual areas of the brain after brief periods of visual deprivation. Philpot said the observation that the brain defect could be reversed "is very encouraging, as it suggests that viable behavioral or pharmacological therapies are likely to exist."
"By showing that brain plasticity can be restored in Angelman syndrome model mice, our findings suggest that brain cells in Angelman syndrome patients maintain a latent ability to express plasticity. We are now collaborating to find a way to tap into this latent plasticity, as this could offer a treatment, or even a cure, for Angelman syndrome," said Philpot.
Philpot added, "This same experimental approach could also reveal how brain cells encode information from experiences in other related disorders, such as autism, and may provide a model to find cures for a variety of neurodevelopmental disorders."
University of North Carolina School of Medicine
Preclinical work shows how one gene causes severe mental retardation
Researchers at Duke University Medical Center and the University of North Carolina have discovered in mice how a single disrupted gene can cause a form of severe mental retardation known as Angelman syndrome.
Model for Angelman syndrome developed by University of Texas at Austin biologists
A model for studying the genetics of Angelman syndrome, a neurological disorder that causes mental retardation and other symptoms in one out of 15,000 births, has been developed by biologists at The University of Texas at Austin.
Innovative surgery corrects vision in kids with neurological disorders
Children with cerebral palsy and other neurological problems often have extremely poor eyesight.
How IVF could be causing genetic errors in embryos
The conditions in which embryos are cultured in the laboratory during in vitro fertilisation could be causing genetic errors that are associated with certain developmental syndromes and other abnormalities in growth and development, such as low birth weight.
Non-coding RNAs help silence the mammalian transcription
Dr. Shirley Tilghman and colleagues (Princeton University) lend new insight into the mechanism of genomic imprinting, demonstrating a necessary role for a non-coding RNA transcript in the silencing of an imprinted gene cluster in mice.
More Angelman Syndrome Current Events and Angelman Syndrome News Articles
 |
The Official Parent's Sourcebook on Angelman Syndrome: A Revised and Updated Directory for the Internet Age by ICON Health Publications (Author) This book has been created for parents who have decided to make education and research an integral part of the treatment process. Although it also gives information useful to doctors, caregivers and other health professionals, it tells parents where and how to look for information covering virtually all topics related to angelman syndrome (also Happy Puppet Syndrome), from the essentials to the most advanced areas of research. The title of this book includes the word official. This reflects the fact that the sourcebook draws from public, academic, government, and peer-reviewed research. Selected readings from various agencies are reproduced to give you some of the latest official information available to date on angelman syndrome. Given parents' increasing sophistication in using the... |
 |
Angelman Syndrome (Clinics in Developmental Medicine) by Bernard Dan (Author) This book provides a comprehensive review of clinical and genetic issues, natural history, possible pathophysiological pathways, specific clinical problems (motor impairment, behaviour, learning difficulties, communication, sleep, epilepsy), clinical neurophysiology, neuropathology, rehabilitation and basic research in the field of Angelman syndrome. This condition is a neurogenetic disorder characterised by developmental delay, absence of speech, motor impairment, epilepsy and a peculiar behavioural phenotype. It is caused by the lack of expression of the UBE3A gene associated with various abnormalities of chromosome 15q11-13. Angelman syndrome appears to be distributed equally worldwide. Precise diagnosis carries clinical and genetic counselling implications. However,... |
 |
Finding Glory in the Thorns: Hope & Purpose in Life's Painful Seasons by Lisa Jamieson (Author), Larry Jamieson (Author) This is a book for anyone who has ever wanted to experience more love, hope, and joy. And for those in the midst of crisis, it presents life-changing opportunity. Is a medical diagnosis, job loss, financial crisis, or other challenge threatening to change your life or steal your dreams? Do you wonder if your life will ever be normal again? Do you sense that a gift lingers in your crisis? Are you overwhelmed with the need for joy or rest? When a family is thrust into a life-altering reality autism, brain injury, cancer, multiple sclerosis, stroke, job loss, financial hardship, marriage breakdown, or other crisis the pain, uncertainty, and exhaustion can seem too much to bear. Sometimes the thorns in our lives even feel like torture. Many of us live in a tug-of-war of... |
 |
Angelman Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References by Icon (Creator) In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading." Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing.This book was created for medical professionals, students, and members of the general public who want to conduct medical research using the most advanced tools available and spending the least amount of time doing so. |
|
Newsletter of the Canadian Angelman Syndrome Society by Cndn Angelman Syndrome Soc Organization helping individuals with AS and their families achieve the optimum quality of life through education and interactive support, and helping others start their own local chapters, by providing bylaws and instructions. Membership comes with a quarterly publication, CASS Newsletter. | |
|
Psychopharmacologic interventions for fragile X: Prader-Willi, Angelman's syndrome.(Behavioral Pediatrics): An article from: Pediatric News by Ben Van Houten (Author) This digital document is an article from Pediatric News, published by International Medical News Group on February 1, 2004. The length of the article is 519 words. The page length shown above is based on a typical 300-word page. The article is delivered in HTML format and is available in your Amazon.com Digital Locker immediately after purchase. You can view it with any web browser. Citation Details Title: Psychopharmacologic interventions for fragile X: Prader-Willi, Angelman's syndrome.(Behavioral Pediatrics) Author: Ben Van Houten Publication: Pediatric News (Magazine/Journal) Date: February 1, 2004 Publisher: International Medical News Group Volume: 38 Issue: 2 Page: 30(1) Distributed by Thomson... | |
 |
Angelman Syndrome - A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers by Philip M. Parker (Author) In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading." Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Angelman syndrome is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to conduct medical research using the most advanced... |
 |
12 Inch Scooter Board with Handles by Fun and Function Handles help kids grip this sturdy plastic scooter with greater ease and balance. Develops strength of the upper and lower extremities and can be used in a sitting, kneeling or prone position for prone extension. Supports motor planning and vestibular activities. Non-marring rubber swivel casters. Assorted colors. 12"x12". |
|
Angelman syndrome: An entry from Thomson Gale's Gale Encyclopedia of Genetic Disorders, 2nd ed. by Jennifer, MS, CGC Roggenbuck (Author) Information on many genetic disorders, and the frequent new findings on them, has been extremely difficult to come by—until now. The “Gale Encyclopedia of Genetic Disorders” addresses the need for current, hard-to-find facts on emerging discoveries. The two-volume Encyclopedia, presented in a single alphabetical sequence, provides clear, complete information on genetic disorders, including conditions, tests, procedures, treatments and therapies, in articles that are both comprehensive and easy to understand, in language accessible to laypersons. The articles are arranged in a standardized format for quick comparison and ease of use, while non-disorder topics are covered in detail with extended entries. Students will want to consult the “Gale Encyclopedia of Genetic Disorders”... | |
 |
Fun and Function's Spiky Tactile Cushion - 13 inches by Fun and Function Our Spiky Tactile Cushion is a wonderful tool to work on balance and postural training with lots of tactile input! The cushion features one side covered with tactile "spikes" about 1/4 inch apart and the other side covered with smooth slightly raised "bumps". Increase or decrease the amount of air you place inside for the perfect seating arrangement. 13 inch diameter. Requires simple hand pump to inflate see: BL1850 |
| © 2009 BrightSurf.com |