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Neuroscientists face a major hurdle in developing drugs to treat brain disorders: if drugs work really well on mice, they often fail when humans are treated. New study suggests potential reason: Brain cells in mice activate genes that are very different from those in human brain cells.
Mice and humans have brains preserved during evolution, which means that they have very similar brain architectures made up of similar brain cell types. In theory, this makes mice ideal test subjects for neuroscientists, who generally do not have the ability to scrutinize the living human brain.
Yet for mysterious reasons, treatments that have worked wonders in the mouse brain often do not work well when they are tested in humans.
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To understand why, a group of scientists from the Allen Institute for Brain Science in Seattle analyzed brains given to deceased people and brain tissue donated by patients with epilepsy after a brain operation . They specifically examined a part of the brain called the medial temporal gyrus, involved in language processing and deductive reasoning.
The researchers sorted out nearly 16,000 cells from this brain region and identified 75 different cell types. When they compared human cells to a set of mouse cell data, they found that their mice had similar counterparts to almost all human brain cells.
But when they examined which genes were activated or deactivated inside these cells, they found clear differences between murine and human cells.
For example, serotonin is a neurotransmitter – or brain chemical – that regulates appetite, mood, memory, and sleep. To do this, it binds to brain cells via a receiver located on the surface of the cell, which acts as a glove designed to catch a baseball.
The researchers found that mouse serotonin receptors were not on the same cells as in humans. Thus, a drug that increases serotonin levels in the brain, such as those used to treat depression, could deliver it to very different cells in mice compared to humans.
They also found differences in gene expression that help link neurons. In essence, the cell track map of our brain can be very different from that of a mouse.
"In the end, there are great similarities and differences between our brain and that of the mouse," co-authored with lead author Christof Koch, chief scientist and president of the Allen Institute for the science of the brain, said in a statement. "One of them tells us that there is a great continuity in evolution, and the other tells us that we are unique."
"If you want to cure diseases of the human brain, you must understand the unique nature of your brain," he added. The results were published yesterday (August 21) in the newspaper Nature.
Originally published on Science live.
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