Research on worms may provide insight to Parkinson’s disease

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Batil Joselevitz

Professor Jon Pierce-Shimomura’s research on C. Elegans worms has made it possible for scientists to study Parkinson’s disease. Shimomura discovered that C. Elegans and humans have difficulty initiating and switching motor abilities when lacking dopamine.

Henry Clayton Wickham

Editor’s note: This is part of a biweekly series showcasing some of the many fascinating projects undertaken by UT faculty.

Professor Jon Pierce-Shimomura’s discovery in the area of Parkinson’s disease research suggests that, as humans, we have more in common with the world’s simplest worms than we might think. By figuring out how C. elegans worms exhibit the symptoms of Parkinson’s disease, Pierce-Shimomura has made it possible for scientists to study Parkinson’s with the worm for the first time. Research with C. elegans is extremely time and cost efficient, as well as simpler compared to current Parkinson’s test subjects like mice.

The Daily Texan: So, historically what role have C. elegans worms played in scientific research?

Jon Pierce-Shimomura: In the 1960s, scientists decided to use this tiny worm called C. elegans to study the genetic basis for development of an organism in general. They were interested in how nervous systems and brains are wired to compute behavior and wanted something simple to work with, so they tried to think of the simplest animal, and they came up with this tiny worm that’s only a millimeter long.

DT: So, what’s happened to make Parkinson’s research possible with the worms?

Pierce-Shimomura: Since I’ve arrived at UT, we’ve been studying the way worms switch between what we think are the equivalent of “gaits.” Most animals have at least two gaits. Humans can walk or run. Horses actually have more than two; they gallop, walk, trot … Even simple animals have two gaits, so I had faith that these critters were more sophisticated than people gave them credit for.

We discovered that the worms have a swimming gait. People hadn’t studied them swimming before. It turns out the worms that lack dopamine can crawl fine and they can swim fine, but when they try to switch from swimming to crawling they freeze up for about a half hour, much like how a person with Parkinson’s would freeze up when they try to switch between a motor program.

People with Parkinson’s disease have a problem with initiating or switching between motor functions. When you walk to this doorway here, you take for granted that you can continue through it. If you’re a doctor and your patient is coming in and they’re newly diagnosed with Parkinson’s disease, often times they’ll walk up fine and then they’ll just freeze in the doorway. This is because our brain needs a little squirt of dopamine to switch to a different motor program when walking through the door. When we go through life, we switch through these programs very smoothly, and we take for granted we can do it, but without dopamine you can’t.

DT: So, the worms and humans kind of use dopamine in the same way?

Pierce-Shimomura: Yes. It looks like this neuronal logic for using dopamine to switch between motor program was hardwired over a billion years ago, even in tiny nematodes, and once evolutions comes up with an answer it doesn’t usually change. Both human and simple creatures like sea slugs, leeches and lampreys use dopamine to switch between motor programs

DT: So how are you applying this discovery to Parkinson’s research?

Pierce-Shimomura: Now we study neural mechanisms for switching between gaits. There are two main strategies we used to try to figure out how to repair the worms. One idea is to treat them with drugs and see if they can move again. It doesn’t take a genius to do this. Parkinson’s disease is a huge problem. There are over a million people with Parkinson’s disease in the U.S. right now, and there is no effective long term treatment or cure.

The next step is, what do you do once the neurons are already dead? What do you do for those people? That’s something that were now investigating. The idea here is that we have these Parkinsonian worms that become rigid when they try to come out of some puddle, so we pre-treat them drugs and see if the drug-treated worms cam move once they come out of puddle. If we’re lucky, we will find a solution that will be applicable to mammals or humans, and we’ll pass the baton to our friends that work with mice and see if it works there.