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."
Other authors are, from Philpot's UNC lab: Thorfinn Riday, graduate student; Adam Roberts, Ph.D., postdoctoral fellow; Danilo Bernardo, medical student; and Rohit Prakash, former M.D./Ph.D. rotation student. Kathryn Condon, a graduate student in Ehler's lab and the department of neurobiology at Duke University; and Richard Weinberg, Ph.D., professor of cell and developmental biology at UNC, also participated in the research.
Support for the work came from grants from the National Institutes of Health, the Howard Hughes Medical Institute, the Angelman Syndrome Foundation and the Simons Foundation.
Les Lang | EurekAlert!
Further reports about: > Angelman syndrome > Neocortex > UBE3A > UNC > balance disorders > brain cell > brain plasticity > chromosome 15 > cognitive abilities > cognitive deficits > developmental disorder > hand flapping > impaired brain plasticity > learning deficits > mental retardation > mouse model > neurogenetic disorder > sleep disturbance > synaptic plasticity > visual areas > visual deprivation
The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft
Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.
Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
19.09.2017 | Event News
19.09.2017 | Physics and Astronomy
19.09.2017 | Power and Electrical Engineering