What is your doctor doing with this information to get you recovered? Or does your doctor not know about this and doesn't care to learn?
A new map of the human brain offers insights, clues to future treatments.
In 21 papers published as a package Thursday, researchers have provided a new map of the human brain, refining the resolution, as one scientist described it, from a rough outline of a shoreline to a satellite view with topography.
They're still far from a GPS guide to what's inside our skulls. However, the new brain cell atlas offers more guidance for researchers desperate to find effective treatments for a wide range of disorders, including addiction, schizophrenia and Alzheimer's.
The studies are part of the National Institute of Health's BRAIN Initiative Cell Census Network, a five-year program launched in 2017 to create a catalog of brain cell types.
In the new studies, published Thursday in "Science" and related journals, the researchers identified more than 3,000 kinds of cells ‒ an order of magnitude beyond what scientists have known before.
"It's the most complex cellular organ and we just haven't had this basic understanding," said Ed Lein, a senior investigator at the Allen Institute for Brain Science, who helped lead several of the studies. "If we don't have a good understanding of the system, we're not going to be able to treat diseases, to understand what really goes wrong."
Implications for disease research
These new maps are particularly useful for understanding the territory of brain diseases such as cancer, said Sten Linnarsson, a leader of some of the research and a professor of molecular systems biology at the Karolinska Institute in Sweden.
Cancer cells follow the same genetic programs found in normal brain cells, but in a distorted way, he said. Some cancer cells seem to repeat the pattern of early brain development, almost growing a new brain within a brain, he said. In other cancer cells, genes involved in wound healing are turned on, as if the brain senses there is something wrong and activates repair mechanisms.
We can get clues about how brain tumors behave, Linnarsson said, by comparing a brain with cancer to the "very organized architecture of the healthy, normal brain and brain development."
Some of that was understood before, he said, but now researchers have a much higher resolution and more systematic map with a lot more cell types. Before, scientists could identify that there were cells called astrocytes involved; now, they can identify different kinds of astrocytes in different parts of the brain operating with different genetic programs.
"It will be the job for future work to figure out what that means for disease," Linnarsson said.
Bing Ren, another research leader, said the brain atlas will allow researchers to compare healthy brains to the brains of people with neurological disorders, including schizophrenia, Alzheimer's and addiction, and could eventually lead to advances in diagnoses and treatment.
Understanding which cells are involved and which genes are turned on and off in different brain conditions should allow more precise diagnoses for disorders that are now mainly identified by their symptoms, said Ren, also a professor at the University of California, San Diego. It can be difficult to test drugs for conditions like autism for which there is no objective diagnosis or measure of improvement; genetic analysis could provide that measure.
"The goal of the brain initiative is to really break that barrier and gain a fundamental understanding of the complex neurological disease mechanisms and to begin to develop strategies to mitigate such disorders," Ren said.
Delving deep into the brain
Just as sequencing the human genome was only the beginning of being able to understand the role of genes, so this map is just the first step toward understanding the brain, Ren said. "Interpreting the information is now the hard part."
Every human brain has roughly 200 billion neurons ‒ the brain cells that send electrical signals.
When he was in college in the ’90s, Ren said, he was taught there were two types of neurons. In his new study, in which he and his colleagues examined 1.1 million brain cells, they found more than 90 different types of neurons ‒ but he suspects there might be thousands. "And we don't have a very good idea of what they are and what they do."
Plus, neurons are only one type of brain cell. Non-neuronal cells outnumber neurons by 5 or 10 to 1.
"We are looking at complicated brain maps and trying to gain a first glance of the variety of the cell types in the human brain in terms of their cell type identity, in terms of their anatomic locations and in terms of their connections among each other," he said. "That's a monumental job. We have to do it step by step."
Where the brains come from
Most brain research is done on tissue from people who agree to donate their brains after death.
Some of the studies in this package were also conducted on tissue donated by living patients who had brain surgery for epilepsy or cancer.
Laboratory tools now exist to enable never-before feasible genetic analysis of living tissue, said Lein from the Allen Insitute.
"Part of what this package (of studies) is about is showing that the modern tools of the field that are normally only used in mouse can all now be applied to human," he said. "It kind of opens up a whole new era of human neuroscience research where we can ask questions at a whole different level of granularity than has ever been possible."
How our brains compare to our cousins'
Several of the papers compared the human brain to the brains of our closest animal cousins, chimpanzees, gorillas, rhesus macaques, and common marmosets. Cell types are similar across primate brains, the studies found, but genetic activity differs among species.
"The genes that really differentiate us from our closest relatives are related to the wiring of the brain and the function of neurocircuits," Lein said.
Evolution has sped up a bit in humans relative to primates, said Dr. Trygve Bakken, another Allen Institute researcher involved in the work. The chimpanzee brain looks more like a gorilla brain than a human brain, even though chimps are more closely related to us than gorillas, he said, suggesting we have evolved faster than chimps.
Studies of mice have dominated brain research so far, Lein said. The human brain is 1,000 times bigger, making it much harder to study, he said, “but we now have the tools that can tackle its complexity directly.”
What remains to be done
Researchers are still considering the brain atlas they released this week as a "draft" because they have so much more work to do.
So far, they have only looked in detail at 42 regions within three human brains.
They intend to look at many more brains, exploring, for instance, how much brains vary from person to person and by sex, age, race and other groupings. The brain cancer glioblastoma, for instance, is much more common among males than females, but researchers don't understand why, Linnarsson said.
He also hopes future work will enable teams like his to locate cells precisely in the brain, "so we know exactly where they are and who are their neighbors," he said. "That's a big part of what we're missing. We don't understand the architectural dynamics: How is (a tumor) growing, what are different cell types doing, how do they relate?"
Now that they have a reference for these three "normal" brains, researchers can compare diseased brains against them, asking what is different. Insights into those differences can lead to new treatments, the scientists said.
"As a field, we're not really making a whole lot of progress on developing new therapies or certainly not cures for brain diseases," Lein said, in part, because researchers haven't really known what's going on inside the brain. "You need to understand this level of granularity … We're really creating a whole new level of inquiry that can be done in the human brain."
Contact Karen Weintraub at kweintraub@usatoday.com.
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