On the outside of our bodies, we look fairly symmetric, NYU Abu Dhabi Associate Professor of Chemistry Timothy Dore explains. "We have two hands that are mirror images of each other, two eyes, and a nose and a mouth in the center. But internally, things are not so balanced. Your heart is a little to the left side; your aortic arch extends from the left to the right in your chest cavity; your liver is on the right side. So, internally, your organs are not symmetrically arranged."
This characteristic, called left-right asymmetry, is established very early on in the development of the embryo, and the neurotransmitter serotonin plays an important role in its establishment. Dore and his colleagues report in the December 19 issue of the journal Chemistry & Biology a new tool for studying the role serotonin plays in the development of left-right asymmetry and the neurotransmitter's role in other physiological functions.
Serotonin does many things: it influences appetite, memory, learning, pain, and mood. Some drug treatments alter the way serotonin works in the brain. For instance, anti-depressant drugs like Prozac and Zoloft are in a class of pharmaceuticals called selective serotonin re-uptake inhibitors, or SSRIs. These drugs increase the level of serotonin in the synaptic cleft between neurons by preventing serotonin from being absorbed back into the brain.
Since serotonin plays a role in many different brain functions, Dore and his team wanted to develop ways to turn serotonin signaling on and off in an organism. "In my laboratory at NYUAD, we are interested in developing photochemical switches — these are switches that can be turned on by applying light. So, using our technology, we built a chemical compound that is composed of a photosensitive switch and serotonin," Dore said. The photosensitive switch is attached to serotonin through chemistry by a covalent bond.
"When we attach the light-sensitive molecule to serotonin, the serotonin becomes inactive. But when we shine light on this light-sensitive molecule — or what's more technically known as a photo-removable protecting group (PPG) — the light breaks the bond between the PPG and the serotonin and the serotonin is released in its active form," Dore explained. Once the PPG releases the serotonin, the PPG becomes "an innocent bystander" in the organism, while the serotonin functions in the way it normally would.
Though other work has been done on this topic, Dore and his team have done something novel. "One thing that's different about our technology is that it can utilize a non-linear optical process called two-photo excitation, which is a way of very tightly controlling within three dimensions the volume of which a particular cargo — in this case serotonin — is released," Dore said.
This is important because the location in which a neurotransmitter is released in the brain influences the signal the neurotransmitter causes. "Imagine a neuron and its dendritic tree," Dore said. "If you can pinpoint the release of the neurotransmitter on one dendrite, you might get a different result than you would by releasing the neurotransmitter at another dendrite. We haven't demonstrated the use of two-photon excitation for activating the serotonin in an organism yet, but we have done it in a chemistry context."
Dore hopes that with more work being done on the topic, the compound they created could help scientists get a better understanding of the causes of seizures and the role serotonin plays in that process. "Much of this project was driven by our desire to understand how coherent neural activity — like an epileptic seizure — propagates through the brain. Serotonin plays an important role in that process," Dore said.