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New clue to autism found inside brain cells
The problems people with autism have with memory formation, higher-level thinking and social interactions may be partially attributable to the activity of receptors inside brain cells, researchers at Washington University School of Medicine in St. Louis have learned.
Scientists were already aware that the type of receptor in question was a potential contributor to these problems -- when located on the surfaces of brain cells. Until now, though, the role of the same type of receptor located inside the cell had gone unrecognized. Such receptors inside cells significantly outnumber the same type of receptors on the surface of cells.
The receptor under study, known as the mGlu5 receptor, becomes activated when it binds to the neurotransmitter glutamate, which is associated with learning and memory. This leads to chain reactions that convert the glutamate's signal into messages traveling inside the cell.
In the new study, scientists working with cells in a dish linked mGlu5 receptors inside cells to processes that turn down the volume at which brain cells talk to each other. These volume changes, essential for learning and memory, may become exaggerated in people with autism.
Pharmaceutical companies have developed therapeutic compounds to decrease signaling associated with the mGlu5 receptor, moderating its effects on brain cells' volume knobs. But the compounds were designed to target mGlu5 surface receptors. In light of the new findings, the scientists question if those drugs will reach the receptors inside cells.
"Our results suggest that to have the greatest therapeutic benefit, we may need to make sure we're blocking all of this type of receptor, both inside and on the surface of the cell," said senior investigator Karen O'Malley, PhD, professor of neurobiology.
The findings, published March 25 in The Journal of Neuroscience, also add a significant new dimension to basic brain cell function. Scientists have long assumed that brain cell receptors are only active on the surface of cells. The new study shows that receptors can be active inside cells, and their effects can be considerably different from the same receptors located on the cell surface.
"The traditional wisdom was that receptors inside the cell were either waiting to go to work on the surface or had just finished working there," said O'Malley. "But when we compared how much of the mGlu5 receptor was on the surface of cells to how much was inside it, we were seeing so much more receptor inside the cell -- at least 50 percent, and in some cases as much as 90 percent -- that we wondered if the interior receptors had separate functions."
In earlier studies, O'Malley and her collaborators showed that mGlu5 receptors on the cell surface sent completely different messages than the same receptors inside the cell.
The scientists knew that most autism studies were conducted with compounds that blocked mGlu5 receptors but could not get into the cell. To determine whether blocking inside receptors would have different effects, O'Malley collaborated with Yukitoshi Izumi, MD, PhD, research professor of psychiatry, and Charles F. Zorumski, MD, the Samuel B. Guze Professor and head of the Department of Psychiatry, who study cell-based models of learning and memory.
When the scientists examined these model systems using compounds that allowed them to activate only mGlu5 receptors within cells, they found that these receptors played a bigger role in turning down the volume of brain cell communications than did the cell surface receptors.
In the last few years, scientists have found that 20 or more types of brain cell receptors located on cell surfaces also are present at high levels inside cells, O'Malley noted.
"This should be a factor we consider when we design drugs to target brain cell receptors," she said. "Do we want to reach cell surface receptors, receptors inside the cell or both?"
Note: Material may have been edited for length and content. For further information, please contact the cited source.
Washington University in St. Louis press release
Publication
C. A. Purgert, Y. Izumi, Y.-J. I. Jong, V. Kumar, C. F. Zorumski, K. L. O'Malley. Intracellular mGluR5 Can Mediate Synaptic Plasticity in the Hippocampus. Journal of Neuroscience, Published March 26 2014. doi: 10.1523/JNEUROSCI.3451-13.2014
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Founded by Russian entrepreneur Dmitry Itskov in February 2011 with the participation of leading Russian specialists in the field of neural interfaces, robotics, artificial organs and systems.
The main goals of the 2045 Initiative: the creation and realization of a new strategy for the development of humanity which meets global civilization challenges; the creation of optimale conditions promoting the spiritual enlightenment of humanity; and the realization of a new futuristic reality based on 5 principles: high spirituality, high culture, high ethics, high science and high technologies.
The main science mega-project of the 2045 Initiative aims to create technologies enabling the transfer of a individual’s personality to a more advanced non-biological carrier, and extending life, including to the point of immortality. We devote particular attention to enabling the fullest possible dialogue between the world’s major spiritual traditions, science and society.
A large-scale transformation of humanity, comparable to some of the major spiritual and sci-tech revolutions in history, will require a new strategy. We believe this to be necessary to overcome existing crises, which threaten our planetary habitat and the continued existence of humanity as a species. With the 2045 Initiative, we hope to realize a new strategy for humanity's development, and in so doing, create a more productive, fulfilling, and satisfying future.
The "2045" team is working towards creating an international research center where leading scientists will be engaged in research and development in the fields of anthropomorphic robotics, living systems modeling and brain and consciousness modeling with the goal of transferring one’s individual consciousness to an artificial carrier and achieving cybernetic immortality.
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Future prospects of "2045" Initiative for society
2015-2020
The emergence and widespread use of affordable android "avatars" controlled by a "brain-computer" interface. Coupled with related technologies “avatars’ will give people a number of new features: ability to work in dangerous environments, perform rescue operations, travel in extreme situations etc.
Avatar components will be used in medicine for the rehabilitation of fully or partially disabled patients giving them prosthetic limbs or recover lost senses.
2020-2025
Creation of an autonomous life-support system for the human brain linked to a robot, ‘avatar’, will save people whose body is completely worn out or irreversibly damaged. Any patient with an intact brain will be able to return to a fully functioning bodily life. Such technologies will greatly enlarge the possibility of hybrid bio-electronic devices, thus creating a new IT revolution and will make all kinds of superimpositions of electronic and biological systems possible.
2030-2035
Creation of a computer model of the brain and human consciousness with the subsequent development of means to transfer individual consciousness onto an artificial carrier. This development will profoundly change the world, it will not only give everyone the possibility of cybernetic immortality but will also create a friendly artificial intelligence, expand human capabilities and provide opportunities for ordinary people to restore or modify their own brain multiple times. The final result at this stage can be a real revolution in the understanding of human nature that will completely change the human and technical prospects for humanity.
2045
This is the time when substance-independent minds will receive new bodies with capacities far exceeding those of ordinary humans. A new era for humanity will arrive! Changes will occur in all spheres of human activity – energy generation, transportation, politics, medicine, psychology, sciences, and so on.
Today it is hard to imagine a future when bodies consisting of nanorobots will become affordable and capable of taking any form. It is also hard to imagine body holograms featuring controlled matter. One thing is clear however: humanity, for the first time in its history, will make a fully managed evolutionary transition and eventually become a new species. Moreover, prerequisites for a large-scale expansion into outer space will be created as well.
Key elements of the project in the future
• International social movement
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• annual award for contribution to the realization of the project of "Immortality”.