How many glial cells in the brain

Their sole function was thought to be to support the survival of neurons, but like other glial cells, they are turning out to serve much more varied purposes. The sting of a paper cut or the throb of a dog bite is perceived through the skin, where cells react to mechanical forces and send an electrical message to the brain.

These signals were believed to originate in the naked endings of neurons that extend into the skin. Glia were long presumed to be housekeepers that only nourished, protected and swept up after the neurons, whose more obvious role of channeling electric signals through the brain and body kept them in the spotlight for centuries.

But over the last couple of decades, research into glia has increased dramatically. As more scientists turn their attention to glia, findings have been piling up to reveal a family of diverse cells that are unexpectedly crucial to vital processes.

It turns out that glia perform a staggering number of functions. They help process memories. Some serve as immune system agents and ward off infection, while some communicate with neurons. Others are essential to brain development. Glia take many forms to perform their specialized functions: Some are sheathlike, while others are spindly, bushy or star-shaped.

By the s, even the most reputable sources in neuroscience were asserting that there are at least ten times as many glia as neurons in the brain. Because the text also estimated the number of neurons in the brain to be around 1 trillion now considered a huge overestimate , the number of glia are implied to be somewhere between 10 and 50 trillion.

For example, a respectable appraisal of the number of neurons and glia in the brain was published in , and it suggested there are about billion neurons and billion glial cells. The largest number of glial cells reported in a primary research report was billion in These seemingly more accurate estimates, however, were largely ignored. The groundbreaking paper in this respect was published by the Brazilian neuroscientist Suzana Herculano-Houzel and her colleagues in They used the isotropic fractionation method to count neurons and glia in the brain, and ended up with estimates of 86 billion neurons and 85 billion non-neuronal cells which included glia and other cells, like endothelial cells.

This suggested that there were actually fewer glial cells than neurons, which agreed with some of the data obtained earlier. There was a bit of resistance to accepting these numbers at first, as some argued that isotropic fractionation had not yet been validated by comparing its results with those obtained through more well-known cell-counting methods.

Today, most researchers have accepted the data obtained with isotropic fractionation, and the preponderance of the evidence supports the idea that the ratio of glia to neurons is about Historically, they have not been given due credit for the integral roles they play in the brain.

That seems to be changing in recent years, however, as we learn more about the functions of glia. And as we get a more accurate view of all that glia do, we also seem to be letting go of inaccurate estimates of their numbers.

Keywords: cell counts; glia number; glia-neuron ratio; history; human brain; neuron number; quantification.

Abstract For half a century, the human brain was believed to contain about billion neurons and one trillion glial cells, with a glia:neuron ratio of After vigorously shaking the solution to evenly distribute nuclei from neurons and glia, Herculano-Houzel takes several samples of the soup, counts the fluorescing green nuclei in each sample under the microscope and calculates the total number of neuronal nuclei in the solution, which should equal the total number of neurons in that brain region.

Subtracting that number from the total nuclei count tells her how many glial cells that section of brain contained. Herculano-Houzel and her colleagues used this technique to analyze the brains of four deceased men and published their results in they consistently found a whole human brain glia to neuron ratio of almost exactly Specifically, they found that the human brain contains about Their study also suggests that the ratio of glia to neurons differs dramatically from one general brain region to the next.

It's the inverse in the cerebellum, an evolutionarily ancient part of the brain that sits astride the brain stem. According to Herculano-Houzel's study, the cerebellum contains Zooming in even further, her study counted 6.

Gray matter is largely made up of the unmyelinated parts of neurons—neurons that are not sheathed by glial cells—whereas white matter is comprised of axons wrapped in insulating oligodendrocytes. These results might explain why so many early counting studies that only sampled cortical gray matter found a roughly or slightly higher glia to neuron ratio. Overall the cerebral cortex—including both gray and white matter—contains far more glia than neurons, but its outermost gray layer is more balanced.

And the cerebellum's incredible density of neurons balances out the glia to neuron ration throughout the whole brain. When Herculano-Houzel first published her innovative technique in , the main objection was that she had not directly compared it to more typical stereological methods, in which cells are counted in slices of brain tissue.

When her results with whole brains matched counts from different brain regions in previous stereological studies, however, Herculano-Houzel says most critics backed off. Some researchers remain concerned that grinding and dissolving the brain destroys a significant number of nuclei.

Herculano explains, however, that the saline detergent she uses Triton X destroys fatty tissues, like cell membranes, but preserves the protein-rich nuclear membrane. Furthermore, she says, fixing brain tissue in formaldehyde before grinding strengthens the bonds between proteins, making them especially difficult to break.

Other researchers say they are hesitant to trust a method that has not been widely used outside of a single research group.

So far, however, at least seven different research teams in the U. Neurobiologist Ben Barres of Stanford University says he never believed the widely parroted glia to neuron ratio—until he looked into the matter himself. Now, he is certain that glia make up at least 80 percent of cells in the human brain. Here is his main reasoning. The human brain contains a finite number of cells, each of which holds the same amount of DNA about 6. The developing human brain produces most of its neurons within the first trimester of pregnancy, but glia do not finish growing in number until a few years after birth.

By comparing the total amount of DNA in a week-old human brain to the total amount of DNA in an infant's brain, Barres reasoned, one could figure out the glia to neuron ratio. Barres found a study published in that analyzed DNA levels in human brains ranging in age from 10 weeks to seven years. The forebrains which do not include the cerebellum contained about 0. Based on these numbers—and accounting for DNA from blood vessel cells—Barres concludes that growing numbers of glia explain the increase in total forebrain DNA and that glia therefore make up at least 80 percent of cells in the human brain.

Even though Barres is confident in his own unpublished calculations—and intends to write that glia far outnumber neurons in the newest edition of the Principles of Neural Science —he argues that no one has conducted the kind of rigorous study that would definitively answer the question of the glia to neuron ratio once and for all.

Barres envisions a study in which researchers stain whole human brains with just about every known marker for both neurons and glia—making sure to capture as many of the different cell types as possible—before slicing up the brains and meticulously counting the cells in each section.

He says all the necessary tools are available. It is only a matter of funding the project and finding the time for all that counting.