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Brain cell type found to differ between man and mouse

March 24, 2009
Courtesy University of Rochester Medical Center
and World Science staff

An often overlooked type of brain cell em­bod­ies one of very few real­ly basic dif­fer­ences be­tween hu­man and ro­dent brains, sci­en­tists are pro­pos­ing.

Researchers at the Uni­ver­s­ity of Roch­es­ter Med­i­cal Cen­ter in New York found that hu­man as­tro­cytes, cells that were long thought of simply as sup­port cells, are big­ger, faster, and much more com­plex than those in mice and rats.

An iso­lat­ed as­tro­cyte, dyed for clar­i­ty (im­age cour­te­sy Na­than S. Ivey, TNPRC; li­censed un­der un­der the Cre­a­tive Com­mons At­tri­bu­tion 3.0  Li­cense)


“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,” said Nan­cy Ann Ober­heim, a med­i­cal stu­dent at the cen­ter who re­cently com­plet­ed her doc­tor­al the­sis on as­tro­cytes.

The find­ings are pub­lished in the March 11 is­sue of the Jour­nal of Neu­ro­sci­ence. In the stu­dy, Ober­heim and co-authors re­ported 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 as­tro­cytes, pro­to­plas­mic as­tro­cytes, are about 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, who led the stu­dy. “Some peo­ple have thought that it’s simply that a big­ger brain is a bet­ter brain,” but that’s not al­ways true in na­ture.

“It may be that hu­mans have a much high­er brain ca­pacity in large part be­cause our as­tro­cytes are more soph­is­t­icat­ed,” added Ned­er­gaard.

As­tro­cytes had long been con­sid­ered pas­sive sup­port cells, a means to hold the rest of the brain cells to­geth­er, like glue. Med­i­cal stu­dents might spend a few min­utes pon­der­ing the as­tro­cyte be­fore mov­ing on to their flashy coun­ter­parts, neu­rons—brain cells that fire the elec­tri­cal sig­nals cru­cial to pret­ty much ever­ything we do. 

That elec­tri­cal ac­ti­vity 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, were ne­glected in re­search be­cause of a gap in the tools used to study the brain, Ned­er­gaard re­marked. 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 heard noth­ing.

So Ned­er­gaard de­vised a new way to “lis­ten” for as­tro­cyte ac­ti­vity, de­vel­op­ing a la­ser sys­tem to look at their ac­ti­vity by meas­ur­ing the amount of cal­ci­um in­side the cells. Her team made a se­ries of startling find­ings. 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. “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.”

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.


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A type of brain cell long overlooked by researchers embodies one of very few ways in which the human brain differs fundamentally from a rodent’s, scientists are proposing. Scientists at the University of Rochester Medical Center in New York 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. “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,” said Nancy Ann Oberheim, a medical student at the center who recently completed her doctoral thesis on astrocytes. The findings are published in the March 11 issue of the Journal of Neuroscience. In the study, Oberheim and co-authors reported 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 astrocytes, protoplasmic astrocytes, are about 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, 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,” added Nedergaard. Astrocytes had long been considered passive support cells, a means to hold the rest of the brain cells together, like glue. Medical students might spend a few minutes pondering the astrocyte before moving on to their flashy counterparts, neurons—brain cells that fire the electrical signals crucial to pretty much everything we do. That electrical activity 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, were neglected in research because of a gap in the tools used to study the brain, Nedergaard remarked. 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 heard nothing. So Nedergaard devised a new way to “listen” for astrocyte activity, developing a laser system to look at their activity by measuring the amount of calcium inside the cells. Her team made a series of startling findings. 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.” 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.