Why Cells In Mouse Brains Fall Short As Models For Human Drug Development : Shots - Health News A detailed comparison of mouse and human brain tissue found differences that could help explain why mice aren't always a good model for human diseases.
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Subtle Differences In Brain Cells Hint at Why Many Drugs Help Mice But Not People

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Subtle Differences In Brain Cells Hint at Why Many Drugs Help Mice But Not People

Subtle Differences In Brain Cells Hint at Why Many Drugs Help Mice But Not People

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AUDIE CORNISH, HOST:

Another science story now. In mice, it's possible to treat brain disorders like Alzheimer's disease. In people, the same treatments usually fail. Researchers are beginning to understand why. NPR's Jon Hamilton reports on a study that found small but important differences between the brain cells in mice and the cells in our own heads.

JON HAMILTON, BYLINE: Brain cells are a bit like orchids. There are hundreds of varieties, and they can be hard to tell apart. But in the past few years, scientists have developed technology that can quickly identify every type of cell in a bit of brain tissue. Ed Lein of the Allen Institute for Brain Science in Seattle says the key is reading each cell's genetic signature by detecting which genes are switched on.

ED LEIN: In one fell swoop, you can get a more or less comprehensive understanding of all of the different types of cells that make up a brain region.

HAMILTON: Lein says this also makes it possible to compare brain tissue from different species.

LEIN: We now have access to this fine level of resolution in the human brain and the ability to compare across and see how good a model a mouse or a monkey actually is.

HAMILTON: Lein was part of a team that analyzed 16,000 human brain cells taken from a part of the cortex, the brain's outermost layer. Then they compared those cells with cells taken from the same area of a mouse brain. Christof Koch, the Allen Institute's chief scientist, says at first glance, the cells look the same.

CHRISTOF KOCH: In one sense, they're remarkably similar. The number of cell types in a human brain and a mouse brain in similar regions of the cortex are roughly similar.

HAMILTON: A closer look revealed that there were some differences, but Lein says they were subtle.

LEIN: On the other hand, these differences can be really quite profound.

HAMILTON: For example, Lein says, take the genes that allow a cell to respond to the chemical messenger serotonin.

LEIN: They're expressed in both mouse and human, but they're not in the same types of cells, which means that serotonin would have a very different function when released into the cortex of the two species.

HAMILTON: That's potentially a big deal because depression drugs like Prozac act on the brain's serotonin system, so testing these drugs on mice could be misleading. Koch says other subtle differences could help explain why so many experimental brain drugs have helped mice but not people.

KOCH: A lot of neurological diseases, a lot of psychiatric diseases that we're suffering from are due to specific defects in particular types of cells.

HAMILTON: Koch says now researchers have a way to see whether those types of cells act in the same way in mice as in people. Tom Nowakowski of the University of California, San Francisco says the advance is long overdue.

TOM NOWAKOWSKI: The technology finally caught up with what we've been needing to do for probably over 40 years.

HAMILTON: Nowakowski wrote an editorial that accompanied the study, which appears in the journal Nature. He says he's especially intrigued by the finding that cells called microglia have a slightly different genetic signature in mice and people.

NOWAKOWSKI: Those cells are the immune cells of the brain, and you might imagine that studies or insights into neuroimmune disorders, for example, may be vastly affected by this difference.

HAMILTON: These disorders include multiple sclerosis and systemic lupus, and there's growing evidence that microglia also play an important role in Alzheimer's disease, which might help explain why experimental Alzheimer's drugs have helped mice but not people.

Jon Hamilton, NPR News.

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