Working with mice, Johns Hopkins researchers say they have figured out how stem cells found in a part of the brain responsible for learning, memory and mood regulation decide to remain dormant or create new brain cells. Apparently, the stem cells "listen in" on the chemical communication among nearby neurons to get an idea about what is stressing the system and when they need to act.
The researchers say understanding this process of chemical signaling may shed light on how the brain reacts to its environment and how current antidepressants work, because in animals these drugs have been shown to increase the number of brain cells. The findings are reported July 29 in the advance online publication of Nature.
"What we learned is that brain stem cells don't communicate in the official way that neurons do, through synapses or by directly signaling each other," says Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine's Institute for Cell Engineering's Stem Cell Program. "Synapses, like cell phones, allow nerve cells to talk with each other. Stem cells don't have synapses, but our experiments show they indirectly hear the neurons talking to each other; it's like listening to someone near you talking on a phone."
The "indirect talk" that the stem cells detect is comprised of chemical messaging fueled by the output of neurotransmitters that leak from neuronal synapses, the structures at the ends of brain cells that facilitate communication. These neurotransmitters, released from one neuron and detected by a another one, trigger receiving neurons to change their electrical charges, which either causes the neuron to fire off an electrical pulse propagating communication or to settle down, squelching further messages.
To find out which neurotransmitter brain stem cells can detect, the researchers took mouse brain tissue, attached electrodes to the stem cells and measured any change in electrical charge after the addition of certain neurotransmitters. When they treated the stem cells with the neurotransmitter GABA - a known signal-inhibiting product the stem cells' electrical charges changed, suggesting that the stem cells can detect GABA messages.
To find out what message GABA imparts to brain stem cells, the scientists used a genetic trick to remove the gene for the GABA receptor - the protein on the surface of the cell that detects GABA - only from the brain stem cells. Microscopic observation of brain stem cells lacking the GABA receptor over five days showed these cells replicated themselves, or produced glial cells - support cells for the neurons in the brain. Brain stem cells with their GABA receptors intact appeared to stay the same, not making more cells.
Next, the team treated normal mice with valium, often used as an anti-anxiety drug and known to act like GABA by activating GABA receptors when it comes in contact with them. The scientists checked the mice on the second and seventh day of valium use and counted the number of brain stem cells in untreated mice and mice treated with the GABA activator. They found the treated mice had many more dormant stem cells than the untreated mice.