January 24, 2006
Robert Packard Center ALS News Network

http://www.alscenter.org/news/briefs/060123.cfm

The best news science could offer the ALS field, most agree, would be finding how to prevent the disease. But what if, in the meantime, a new method appears that could stop ALS in progress? In medical research, only the unwise put their hopes in a single outcome. That's why, among its approaches, the Packard Center's work addresses possibilities of halting the disease and restoring or, at least, improving an ALS-damaged nervous system and musculature.

Last month, Packard scientist Hongjun Song reported findings that could shed light on central nervous system repair [see press release: NEW NEURONS TAKE BABY STEPS IN THE ADULT BRAIN http://www.alscenter.org/news/press/051222.cfm]. As reported in the journal Nature, a Johns Hopkins team led by Song clarified how the adult brain's newest neurons become integrated into existing circuits - a key step in their becoming useful cells. Such work is foundational if you're trying to develop a stem cell therapy.

The studies, done in mice, focus on the hippocampus, one of few areas in the brain to generate nerve cells throughout life. First, Song's team showed that a brain chemical called GABA readies "newborn" neurons for future connections with the more mature ones already in circuits. "We know GABA is important during fetal development of the nervous system," says Song, "but we've shown that it's also important in adults." Specifically, nerve activity within the hippocampus creates a wash of GABA which excites the new neurons - a required first step.

Next, Song's team found, existing mature nerve cells make connections - synapses - with the primed baby neurons. The first ones to connect, interestingly, use GABA as their chemical messengers. That means the newborn neurons, in addition to experiencing a constant barrage of GABA, also sense the messenger in pulses typical of brain circuits. The third and final step occurs when the new neurons synapse with mature neurons that communicate via another chemical, the critical excitatory messenger glutamate.

"These steps essentially shift neurons from a new, developmental state to becoming adult cells," says Song. "Initially, they're excited by a flood of GABA, but by the time they're fully integrated, the neurons respond to GABA and glutamate like the adult neurons around them."

It will take more research to discover whether stem cells introduced into a damaged central nervous system behave as newborn neurons but, the scientists say, such studies as theirs could improve techniques to insure that introduced cells will "take" in the nervous system. More study will also reveal if introduced stem cells enhance the existing natural process of new neuron production and integration.

The study, first published in Nature online on December 11, 2005, was funded by The Packard Center for ALS Research at Johns Hopkins, the National Institutes of Health, the Klingenstein Fellowship Awards in the Neurosciences and the Whitehall Foundation.

Shaoyu Ge, Eyleen L.K. Goh, Kurt A. Sailor, Yasuji Kitabatake and Guo-li Ming, all of Johns Hopkins, were part of the research team.