Sections of neurons captured with new imaging technology from Stanford researchers., November/December 2010  —  While large pharmaceutical companies like Pfizer, Eli Lilly and Bristol-Myers Squibb spend millions of dollars pursuing new treatments for neurological diseases like Alzheimer’s, a huge impediment to their success lies in the fact that the brain and diseases affecting it are still not well understood. As my colleague Bob Langreth has pointed out several times, including here, there is still quite a bit of controversy about what causes Alzheimer’s.

New research by scientists at Stanford University may help to change that. The researchers created a state-of-the-art imaging system and used it to look at brain tissues of mice (see the photo at right) –and were able to quickly and accurately count the high number of connections between the brain’s nerve cells with a level of detail not attained before. The research results were published today in the journal Nature.

There are some 200 billion nerve cells (neurons) in the brain, linked together by trillions of contacts called synapses. “In a human, there are more than 125 trillion synapses just in the cerebral cortex area [a thin layer of tissue on the brain’s surface],” said Stephen Smith, PhD, a professor of molecular and cellular physiology and a senior author of the new research paper. Smith said that up to now, scientists have been guessing when they attempt to map the circuitry of the cerebral cortex. The synapses in the brain are smashed so close together that traditional microscopes couldn’t make them out. “Now we can actually count them and, in the bargain, catalog each of them according to its type.”

The method Smith and others in his lab developed is called array tomography. The researchers took slabs of tissue from a mouse’s cerebral cortex, sliced it into sections 70 nanometers thick, stained them with antibodies designed to match certain proteins and attached molecules that responded to glowing light.

After taking very high resolution photographs of the tissue slices, the information in the photos was virtually stitched together using new computational software designed by study co-author Brad Busse. The result: Researchers could move through a 3-D mosaic created by the software. Different colors represent different synaptic types.

The promise is great, and the researchers are optimistic. “I anticipated that within a few years, array tomography will have become an important mainline clinical pathology technique and a drug research tool,” said Smith. Let’s hope that it ultimately leads to unraveling the many mysteries of crippling neurological diseases like Alzheimer’s.


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