DOPAMINE SIGNALING

Dopamine is a neurotransmitter that modulates and affects the function of various parts of the brain and body. It has been linked to the mechanisms involved in movement, cognition, pleasure, motivation, and learning. The importance of dopamine was revealed by stem cell research, neuroscience, but especially by Michael J. Foxx’s affliction with Parkinson’s, a neurodegenerative disorder caused by insufficient dopamine in the brain. In Erik M Jorgenson’s Dopamine: should I stay or should I go now?, he summarizes the findings made by Daniel Chase on dopamine signaling.

Research has demonstrated that dopamine signaling can act synergistically as well as antagonistically in vertebrates. Chase and colleagues wanted to verify this in the roundworm, Caenorhabitids Elegans as well as find the downstream components involved in the signaling pathway of the receptors. C. Elegans is a transparent nematode with every neuron known and mapped out. This makes C. Elegans good model for neurological experiments. There are three dopamine receptors, dop-1, dop-3, and dop-4 involved in locomotion behavior of these worms. Dop-1 reacts to dopamine by giving the green light for the worms to go while dop-3 tells the worm to stop. Worms with their dop-1 gene knocked out did not have any observable change in phenotype, but worms that had their dop-3 gene knocked out did not slow down when encountering food and were very resistant to paralysis by too much dopamine. When worms had both dop-1 and dop-3 knocked out, they did respond to food by slowing down and were paralyzed by excess dopamine indicating that another dopamine receptor, dop-4, contributed to locomotion behavior. These similar effects on the worm may be caused by both dop-1 and dop-3 acting on the same signaling pathway not by each receptor having its own pathway. The researchers wanted to know more about the signaling pathway and screened the worms for mutants to identify the downstream components. They found that “dopamine would bind D1-like DOP-1 receptors and activate G q, and also bind D2-like DOP-3 receptors, which would antagonize D1 function through activation of G o.” (Jorgenson)

These findings by Chase take us a step closer to understanding dopamine receptors and their role in regulating motor neurons. Jorgensen’s says, “Dopamine’s antagonistic effects on the same cells can provide the cell with more sensitive regulation.” Hopefully with further research, we might be able to find ways to gain access to the system and regulate dopamine and dopamine receptors with drugs and treatments for disorders involving dopamine.

Dan Chase is a recent addition to the faculty in the Biochemistry and Molecular Biology, and Neuroscience departments.


Q&A
Q: Why is it that by using C. elegans we can compare what happens to that species and then make connections to our own?
A: It is believed that the basic mechanisms are highly conserved so that the signaling pathway will be the same or similar to that in humans or at least give insight and understanding of dopamine receptors. Like how the study of a squid neuron led to discoveries about how neurons work in general or the DNA helix is generally the same throughout species, but what changes are perhaps length, specialization, and coding.

Q: What else is going on in his lab and what he plans on doing with the results?
A: Currently there are four undergraduates, a research assistant, and 2 graduate students, each with a project. I am looking further into the signaling pathway of dop-3 while others are also expanding on his research in the paper as well as other dopamine signaling projects.


---happyfeet