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Here's the reason why drugs that work so well in mouse brains often fail miserably in humans



Neuroscientists are faced with a major obstacle to the development of drugs to treat brain disorders – when the drugs are effective in mice, they are often not well considered in the treatment of humans. Now a new study suggests a possible reason: Brain cells in mice activate genes that are very different from those in human brain cells.

Mice and humans have evolutionarily preserved brains, which means that they have very similar brain architectures made up of similar types of brain cells. Theoretically, mice are therefore ideal subjects for neuroscientists, who normally can not look into living human brains.

For mysterious reasons, however, treatments that work wonderfully in the brain of mice often fail in humans.

Related to: 7 Ways to Explore Your Brain

To figure out why this is possible, a group of scientists from the Allen Institute for Brain Science analyzed in Seattle Donated brains of deceased and brain tissue donated by epileptic patients after brain surgery. Specifically, they examined a part of the brain, the medial temporal gyrus, involved in speech processing and deductive thinking.

Researchers sorted nearly 1

6,000 cells from this brain region and identified 75 different cell types. When comparing human cells to a data set of mouse cells, they found that mice had correspondences that resembled almost all human brain cells.

However, they investigated which genes were switched on or off in these cells. They found strong differences between mouse and human cells.

Serotonin, for example, is a neurotransmitter – or a chemical substance of the brain – that regulates appetite, mood, memory, and sleep. This is done by binding to brain cells via a receptor on the cell surface, which acts like a glove that is used to catch a baseball.

However, the mouse serotonin receptors are not in the same cells as in humans, the researchers noted. A drug that raises brain serotonin levels, as it is used to treat depression, might deliver it to mice in cells that are completely different than humans.

They also found differences in the expression of genes that help build connections between neurons. In essence, the cellular roadmap in our brain can look very different than in a mouse.

"The bottom line is that there are great similarities and differences between our brain and that of the mouse," said co-senior author Christof Koch, chief scientist and president of the Allen Institute for Brain Science, said in a statement . "One of them tells us that there is a great evolutionary continuity, and the other tells us that we are unique."

"If you want to cure diseases of the human brain, you have to understand the uniqueness of the human brain," he added. The results were published yesterday (August 21) in the journal Nature .

Originally published on Live Science .


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