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Better look at tiny mice brains points to bigger things

Better look at tiny mice brains points to bigger things

A new technology is letting researchers see big differences between the tiny brains of male and female mice.

Researchers from Carnegie Mellon University, the University of Pittsburgh and Nashville's Vanderbilt University used three-dimensional magnetic resonance microscopy, or MRM, to see how the puberty hormones influenced mouse brain development.

"No one has ever done a detailed study of the difference between the male and the female [mouse] brain," said investigator Eric Ahrens, of Carnegie Mellon and the Pittsburgh NMR Center for Biomedical Research.

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Nationwide, he added, "there's only a handful of instruments capable of doing this measurement." The findings were recently published in the early online edition of the journal NeuroImage.

Ahrens' team found the brains of the mice were very similar during childhood.

But the high hormone levels of puberty led to dramatic differences between adult males and females in the size of specific brain structures, including those involved with emotion, learning and memory.

For example, the male amygdala, an area known to be associated with aggression, was more than 13 percent bigger than that of the female, the researchers found. Overall brain size was the same between the sexes.

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Spotting meaningful size differences in the substructures of a brain that is less than a half-inch big requires an incredible eye for detail.

Conventional measurement techniques, which involve extracting, preserving, slicing and reconstructing the tissue, are laborious and can take months to complete, so mouse brain studies like Ahrens' are rarely done.

But powerful new technology made it possible to get results within weeks.

Like conventional MRI machines, MRM also uses magnetic fields to take vivid pictures of anatomy, but its magnets are about 10 times stronger, Ahrens said.

"That allows us to image subjects like the mouse brain at really high resolution, at nearly cellular [level]," Ahrens said. "[We] get a quick, accurate representation of the 3D structures in the brain."

Ahrens said MRM machines for humans are being developed.

Human brains are much larger, so researchers have already compared differences between the sexes. But those studies can't account for the myriad factors that influence neurologic development.

"Genetics is known to have an effect on the sizes of certain brain structures in people," Ahrens said. "The other factor you can't control for in humans is rearing."

Lab mice, though, have been inbred to be nearly genetically identical and their living conditions are controlled, adding more weight to the findings, he said.

Scientists typically use mice to learn about neurologic development, diseases, and drug effects that could be applied to humans. Knowing that there are sex-based differences in the mouse brain could help a researcher use the mouse model better.

And some mouse patterns did not parallel human brain development, which could teach researchers more about the limitations of using the animal model, Ahrens noted.

In the future, the researchers might inject mice with opposite-sex hormones to see what happens to brain development.

Ahrens is trying to create agents that tag certain molecules, cells or tissues in the body so that they can be monitored with MRM techniques. Then, doctors might be able to watch stem cells or gene therapy in action, he said.

First Published: July 5, 2004, 4:00 a.m.

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