New Techniques Study The Brain's Chemistry, Neuron By Neuron

Researchers at the University of Illinois at Urbana-Champaign havedeveloped tools for studying the chemistry of the brain, neuron byneuron. The analytical techniques can probe the spatial and temporaldistribution of biologically important molecules, such as vitamin E,and explore the chemical messengers behind thought, memory and emotion.

"In most organ tissues of the body, adjacent cells do not havesignificant differences in their chemical contents," said JonathanSweedler, a William H. and Janet Lycan Professor of Chemistry anddirector of the Biotechnology Center at the U. of I. "In the brain,however, chemical differences between neurons are critical for theiroperation, and the connections between cells are crucial for encodinginformation or controlling functions."

By dismantling a slice of brain tissue into millions of singlecell-size pieces, each of which can be interrogated by massspectrometric imaging techniques, Sweedler's research group can performcellular profiling, examine intercellular signaling, map thedistribution of new neuropeptides, and follow the release of chemicalsin an activity-dependent manner.

Sweedler will describe the techniques and present new results at the230th American Chemical Society national meeting in Washington, D.C.Using these techniques, Sweedler's group has already discoveredmultiple novel neuropeptides in a range of neuronal models frommollusks to mammals.

"We work with sea slugs, whose simple brains contain 10,000neurons; we work with insects possessing one million neurons; and wework with mice having 100 million neurons," said Sweedler, who also isa researcher at the Beckman Institute for Advanced Science andTechnology. "Working with these model organisms allows us to examinethe functioning of such basic operations as the neuronal control ofbehavior and long-term memory."

Sweedler's group also developed an approach for looking at thedistribution of smaller molecules in brain cells. In a paper acceptedfor publication in the Journal of the American Chemical Society, andposted on its Web site, they report the subcellular imaging of vitaminE in the sea slug Aplysia californica.

The researchers utilized novel sampling protocols and single celltime-of-flight secondary ion mass spectrometry to identify and map thepresence of vitamin E in the membranes of isolated neurons.

"To our surprise, we found that vitamin E was not distributed uniformlyin the neuronal membrane," Sweedler said. "Instead, vitamin E wasconcentrated in the neuron right where it extends to connect with otherneurons."

The subcellular localization of vitamin E, which had been impossible toobtain in the past, supports other work that suggested vitamin Eperformed an active role in transport mechanisms and cellular signalingof neurons.

"Our technique doesn't tell us how or why vitamin E is distributed thisway, but suggests that it is under active control and tightregulation," Sweedler said. "Understanding the chemistry that takesplace within and between neurons, including small molecules likevitamin E, will no doubt lead to a better understanding of brainfunction in healthy and diseased brains."

Co-authors of the paper are Sweedler, research scientists Jinju Lee andStanislav Rubakhin, postdoctoral research associate John Jurchen andgraduate student Eric Monroe. The U.S. Department of Energy and theNational Institute on Drug Abuse funded the work.