Release of the neurotransmitter GABA by adult neuronal precursor cells that develop into neurons limits stem cell proliferation, according to a study at Yale School of Medicine in the September issue of Nature Neuroscience.
Tight regulation of new cell growth in the adult brain is critical since uncontrolled proliferation can lead to devastating diseases, such as cancer.
“The GABAergic signaling described in our paper allows a proper balance between stem cells and daughter cells, and prevents out-of-control proliferation of stem cells,” said Angelique Bordey, assistant professor in the Departments of Neurosurgery and Cellular & Molecular Physiology, and senior author of the study. “The next question we would like to answer is what would happen if this signaling was disrupted in a living being.”
Neural stem cells in the subventricular zone of the brain are thought to give rise to glioma, or brain tumors, when their proliferation is out of control, she said. “One of the goals of this line of research is to find ways to promote neurogenesis in a controlled manner, so identifying signaling pathways, factors and receptors that block or promote neurogenesis is very important,” Bordey said. “These factors and receptors provide additional sites for pharmaceutical targets to promote neurogenesis and self-renewal of dying cells.”
Alternatively, identifying negative GABAergic signaling on stem cell proliferation, as the researchers did in this study, suggests that any drugs that would enhance GABA’s function may limit neurogenesis, she said.
“GABAergic drugs such as alcohol and benzodiazepines (some sleeping pills) have been used by a large number of individuals in our society and these drugs are expected to block stem cell proliferation,” Bordey said. “Such an impact of these drugs on neurogenesis and brain function would be the next step to investigate.”
Co-authors include Xiuxin Liu and Qin Wang of Yale and Tarik Haydar of George Washington University School of Medicine.
Nature Neuroscience 8: 1179-1187 (September 2005).
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