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| Of Mouse, Man and Astrocyte: A Distinctive Difference |
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| SciMed - Neuroscience | |||
| TS-Si News Service | |||
| Friday, 27 March 2009 14:00 | |||
 Rochester, NY, USA. A type of  brain cell that was long overlooked by researchers embodies one of very few ways in which the human brain differs fundamentally from that of a mouse or rat, according to researchers at the University of Rochester Medical Center. The mouse (Mus musculus) is the classic model vertebrate, bred and selected for particular traits of medical interest (e.g. body size, muscularity, and obesity). As a model organism, the species is extensively studied with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms, particularly humans.
A great deal of information has been developed from studies of model organisms, but scientists must take care when making generalizations to ensure that resulting hypotheses can withstand real-world testing. In the current research, the scientists found that human astrocytes, cells that were long thought simply to support flashier brain cells known as neurons that send electrical signals, are bigger, faster, and much more complex than those in mice and rats. Their findings appear in the Journal of Neuroscience.
 Brain Cells: Classic Model
Warren McCulloch and Walter Pitts put forth the classic model of how brain cells communicate in 1943.
By that time the first digital computers were envisaged and the McCulloch-Pitts model suggested that brain cells communicate in a binary fashion, represented by a “1” for firing and a “0” for not firing (much as a modern computer functions).
It is common, but imprecise, to say that a mammalian brain functions like a computer. In part, this is because current observations suggest that gap junctions cause “short circuiting” as part of the brain’s normal functions. (A computer could not function if it short circuited.)
It is possible that these short circuits in the mammalian brain generally enhance brain function and adaptation to the environment. This could permit creative thinking, the combining of isolated facts into new ideas.
Additionally, Dr. Jeremy Coplan, a professor of psychiatry at SUNY Downstate –- has proposed that excessive firing of these circuits along gap junctions may play a role in psychosis and mania.
Given such uncertainty, the human brain may have adaptive and management capabilities that exceed current computer technology.
The brain presents things we do not fully understand. New ways of seeing (and understanding) become critical to further advances. glial cells in the brain and spinal cord that perform many functions in human beings.“There aren’t many differences known between the rodent brain and the human brain, but we are finding striking differences in the astrocytes. Our astrocytes signal faster, and they’re bigger and more complex. This has big implications for how our brains process information”
— Nancy Ann Oberheim, Ph.D.Astrocytes had long been considered passive support cells, a means to hold the rest of the brain cells together, like glue. Past research had established that astrocytes provide biochemical support of endothelial cells which form the blood-brain barrier, the provision of nutrients to the nervous tissue, and play a principal role in the repair and scarring process of the brain and spinal cord following traumatic injuries.
Nancy Ann Oberheim and her co-authors discovered a previously unknown form of the cell, a varicose projection astrocyte, in the human brain but not in the rodent brain.
The team also found that the most abundant type of astrocyte, protoplasmic astrocytes, are approximately 2.6 times larger than their rodent counterparts, and that the human cells have about 10 times as many “processes,” or structures designed to connect to other cells.
“We have not really been able to understand why the human brain is so much more capable than that of any other animal,” said neuroscientist Maiken Nedergaard, M.D., D.M.Sc., who led the study. “Some people have thought that it’s simply that a bigger brain is a better brain, but an elephant’s brain is bigger than a person’s, for example, but it’s not nearly as powerful. So that’s not the answer.
 “It may be that humans have a much higher brain capacity in large part because our astrocytes are more sophisticated and have more complex processing power,” added Nedergaard, who spoke at a Gordon Research Conference on glial biology.
“Studies in rodents show that non-neuronal cells are part of information processing, and our study suggests that astrocytes are part of the higher cognitive functioning that defines who we are as humans.”
Medical students might spend a few minutes pondering the astrocyte before moving on to their flashy counterparts, the neurons that fire the electrical signals crucial to pretty much everything we do. It’s the electrical activity of neurons that constitutes what most scientists have considered to be brain activity, and it’s the neurons that are the target of every currently available drug aimed at brain cells. If astrocytes were important, scientists thought, it was most likely because they help create a healthy environment for the neurons.
It turns out that astrocytes, which are 10 times as plentiful as neurons, had been pushed to the boundaries of
neuroscience because of a gap in the tools used to study the brain. Scientists measure signaling among brain cells mainly by looking at electrical activity. But astrocytes don’t fire in the same way as neurons, and so conventional techniques don’t record their activity. So when scientists “listened” with conventional techniques, they witnessed no activity.Rather than realizing their tools were incomplete, scientists assumed that astrocytes were silent.
 So Nedergaard devised a new way to “listen” for astrocyte activity, developing a sophisticated laser system to look at their activity by measuring the amount of calcium inside the cells. Her team has discovered what might be called the secret lives of astrocytes and has made a series of startling discoveries. Astrocytes use calcium to send signals to the neurons, and the neurons respond; neurons and astrocytes talk back and forth, indicating that astrocytes are full partners in the basic working of the brain; and astrocytes are central to conditions like stroke, Alzheimer’s, epilepsy, and spinal cord injury.“Dogma is slow to change, and one of the dogmas of neuroscience is that astrocytes are support cells that don’t do much themselves,” said Oberheim. “The view is slow to change, but scientists are coming around. Astrocytes are now acknowledged as active participants in brain function and sensory processing.”
The brain’s two signaling systems — one composed of neurons, and one of astrocytes — complement each other, Nedergaard said. Neurons send signals extremely quickly over long distances – the hand touches a hot stove, for instance, and the brain detects the danger and moves the hand away, instantly. Astrocytes, in contrast, send slower signals whose function is still being worked out by scientists.
“The brain contains two communication networks using different languages,” said Nedergaard, director of the Division of Glial Disease and Therapeutics of the Center for Translational Neuromedicine. “You have a highly sophisticated electrical network embodied in the neurons, which send signals instantaneously. And then you have a much slower network composed of astrocytes whose signals are 10,000 times slower but which might be able to process the information in a more sophisticated manner and retrieve memories.
“There is no other tissue in the body that mixes up two different types of cells so completely as how astrocytes and neurons are interspersed throughout the brain,” Nedergaard added. “Both comprise extensive signaling networks. Where those networks interface and how they interact makes the brain so interesting.”
The study is one of the most extensive examinations yet of the astrocyte. To do the study, the team studied human brain tissue taken from 30 people who had had surgery, mostly to treat epilepsy or brain tumors. They compared the astrocytes in human brains to those in mice and rats. In addition to the findings above, the team noted additional differences:
FundingThe work was funded by the G. Harold and Leila Y. Mathers Charitable Foundation and by the National Institute of Neurological Disorders and Stroke (NINDS).
ParticipantsThe authors include Steven Goldman, M.D., Ph.D., professor and chair of Neurology; Webster Pilcher, M.D., professor and chair of Neurosurgery; Jeffrey Wyatt, D.V.M., professor and chair of Comparative Medicine; and research assistant professors Takahiro Takano, Ph.D., Xiaoning Han, Ph.D., Wei He, Ph.D., and Fushun Wang, Ph.D.
Other authors include technical associate Qiwu Xu; Jane Lin, Ph.D., of New York Medical College; and Jeffrey Ojemann, M.D., and Bruce Ransom, M.D., Ph.D., of the University of Washington, where Oberheim completed part of her doctoral thesis under Nedergaard’s supervision. CitationUniquely Hominid Features of Adult Human Astrocytes. Nancy Ann Oberheim, Takahiro Takano, Xiaoning Han, Wei He, Jane H. C. Lin, Fushun Wang, Qiwu Xu, Jeffrey D. Wyatt, Webster Pilcher, Jeffrey G. Ojemann, Bruce R. Ransom, Steven A. Goldman, and Maiken Nedergaard. Journal of Neuroscience 2009; 29(10): 3276. doi: 10.1523/JNEUROSCI.4707-08.2009
Abstract Defining the microanatomic differences between the human brain and that of other mammals is key to understanding its unique computational power. Although much effort has been devoted to comparative studies of neurons, astrocytes have received far less attention. We report here that protoplasmic astrocytes in human neocortex are 2.6-fold larger in diameter and extend 10-fold more GFAP (glial fibrillary acidic protein)-positive primary processes than their rodent counterparts. In cortical slices prepared from acutely resected surgical tissue, protoplasmic astrocytes propagate Ca2+ waves with a speed of 36 µm/s, approximately fourfold faster than rodent. Human astrocytes also transiently increase cystosolic Ca2+ in response to glutamatergic and purinergic receptor agonists. The human neocortex also harbors several anatomically defined subclasses of astrocytes not represented in rodents. These include a population of astrocytes that reside in layers 5–6 and extend long fibers characterized by regularly spaced varicosities. Another specialized type of astrocyte, the interlaminar astrocyte, abundantly populates the superficial cortical layers and extends long processes without varicosities to cortical layers 3 and 4. Human fibrous astrocytes resemble their rodent counterpart but are larger in diameter. Thus, human cortical astrocytes are both larger, and structurally both more complex and more diverse, than those of rodents. On this basis, we posit that this astrocytic complexity has permitted the increased functional competence of the adult human brain. The TS-Si News Service is a collaborative effort by TS-Si.org editors, contributors, and corresponding institutions. Sources can include the cited individuals and organizations, as well as TS-Si.org staff contributions. Articles and news reports do not necessarily convey official positions of TS-Si, its partners, or affiliates. We welcome your comments. Use the form below to leave a public comment or send private correspondence via the TS-Si Contact Page. We will not divulge any personal details or place you on a mailing list without your permission.TS-Si is dedicated to the acceptance, medical treatment, and legal protection of individuals correcting the misalignment of their brains and their anatomical sex, while supporting their transition into society as hormonally reconstituted and surgically corrected citizens.
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