Protein Directs Neural Stem Cell Migration

This finding was published in the March 19, 2002, issue of the Proceedings of the National Academy of Sciences.

"Neural stem cells are the precursors to the variety of cell types found in the brain, said Kiminobu Sugaya, assistant professor of psychiatry at the University of Illinois at Chicago (USA) and the study's principal investigator. "Triggered by unknown environmental cues or factors, they migrate to specific areas to become a glial cell or a neuron, forming a link in the adult brain's complex neural network.”

In the study, human neural stem cells were transplanted into an empty space of the brain, called the ventricle, in normal mice and in mice incapable of producing a protein called reelin. The mice are called reeler mice because of their peculiar gait, a result of their genetic defect. "In the reeler mice, the stem cells got lost,” Prof. Sugaya said. "They failed to migrate.”

In the normal mice, however, the cells migrated into the hippocampus, the central processing unit of the brain; the olfactory lobes, controlling the sense of smell; and the cerebral cortex, responsible for higher mental activities like learning, memory, perception and problem solving. Once located in those regions, the cells turned into mature cells capable of functioning in the new environs.

"In normal mice we found a beautiful, symmetrical migration and differentiation of the stem cells,” Prof. Sugaya said.

Not only did this study clearly identify, for the first time, the role of reelin in the adult brain, but it also allowed the researchers to suggest a possible molecular mechanism for schizophrenia, a devastating psychiatric illness characterized by a distorted perception of reality, disordered thinking, and a flat affect. In an earlier postmortem study of the brains of schizophrenics, Erminio Costa, a co-author of the present study, found that the level of reelin was half that in normal human brains. Moreover, in a blind study of 60 brains taken postmortem from individuals diagnosed with severe psychiatric disorders, Dr. Costa was able to correctly identify those that came from psychotic patients by testing for levels of reelin.

"Perhaps in schizophrenics, who lack reelin, the brain's stem cells cannot find their way to make the appropriate neural connections,” said Kiminobu Sugaya, "As a result, perception and thinking may break down.”




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