How neurons control the division of neural stem cells
Neural stem cells "eavesdrop" on the conversations of neurons
LifeSciencesToday based on Johns Hopkins Medicine: Brain's Stem Cells "Eavesdrop" to Find Out When to ActJohns Hopkins School of Medicine scientists have found out how stem cells located in the part of the brain responsible for regulating learning, memory and mood make a decision about whether to stay at rest or start creating new brain cells.
Obviously, stem cells "intercept" chemical "conversations" between neurons in the immediate vicinity. This gives them an opportunity to understand when the system is under stress and when they should start acting.
According to the researchers, understanding this chemical signaling process can shed light on how the brain reacts to the environment and how modern antidepressants work, since in animals these drugs have been shown to increase the number of brain cells. The results of the study are published online in the journal Nature (Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision).
"What we've learned is that brain stem cells don't communicate in the usual way that neurons do– through synapses and direct signaling," says Hongjun Song, PhD, professor of neurology, director of the stem cell program at the Institute for Cell Engineering. "Synapses, like cell phones, allow nerve cells to communicate with each other. Stem cells do not have synapses, but our experiments show that they hear, although not directly, how neurons communicate with each other. It's like listening to someone next to you talking on the phone."
This "conversation" eavesdropped by stem cells consists of chemical messages fed by neurotransmitters released by synapses of neurons – structures that make possible interneuronal communication. Neurotransmitters released by one neuron and perceived by another trigger a change in the electrical charges of the recipient neuron, which causes the neuron to either generate electrical impulses or calm down, interrupting further transmission of messages.
To find out which neurotransmitter brain stem cells can recognize, scientists inserted electrodes into the brain stem cells of mice and measured any changes in their electrical charge after adding certain neurotransmitters. The electrical charges of stem cells changed when they were treated with gamma-aminobutyric acid (GABA), a well–known inhibitory neurotransmitter, which indicated that stem cells can perceive GABA messages.
To find out what message GABA transmits to brain stem cells, scientists genetically removed the GABA receptor gene – a protein on the cell surface – only in stem cells. Microscopic examination of stem cells deprived of GABA receptors for five days showed that these cells replicated, creating glial cells. There were no changes with stem cells having GABA receptors.
The scientists then injected normal mice with valium, often used as a sedative. Like GABA, valium acts by activating GABA receptors. Counting the number of brain stem cells in such mice on the second and seventh days after administration of valium showed a sharp increase in the number of dormant stem cells compared to control group animals.
"Traditionally, GABA orders neurons to shut down and not continue transmitting messages to other neurons," says Professor Song. "In this case, the neurotransmitter also turns off the stem cells and keeps them in a dormant state."
The population of brain stem cells of mice (and other mammals, including humans) is surrounded by at least 10 different types of neurons, and any of these species can keep stem cells at rest. To find out which neurons control stem cells, the researchers embedded photoactivatable proteins in them that cause cells to send an electrical pulse, as well as release a neurotransmitter when light falls on them. By activating a certain type of neurons and observing stem cells with electrodes, they found that the neurons transmitting a signal to stem cells that causes a change in electric charge are parvalbumin–expressing interneurons.
Parvalbumin-expressing interneuron (red) in the hippocampus,
surrounded by numerous adult neural stem cells (green). Photo: Gerry Sun
Finally, to test whether this stem cell control mechanism corresponds to what an animal can experience, the scientists placed normal mice and mice lacking GABA receptors in brain stem cells in stressful conditions, socially isolating them. After a week, the number of stem and glial cells increased in normal isolated mice. No such increase was observed in isolated mice without GABA receptors.
"Communication through GABA undoubtedly conveys information about the effects of brain cells from the outside world, and, in this case, keeps brain stem cells in reserve, so we do not use them if there is no need," concludes Professor Song.
Portal "Eternal youth" http://vechnayamolodost.ru03.09.2012