C. elegans听worms seen under the microscope dyed with fluorescent proteins. (Credit: via )
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A team of biologists and engineers at 精品SM在线影片 recently led an exercise class for tiny worms鈥攁nd their findings could one day help doctors treat humans with Parkinson鈥檚 disease and similar illnesses. 听
The study dives into the incredibly small world of Caenorhabditis elegans. These swimming nematode worms measure just 1 millimeter long. They have only 302 neurons, or nervous system cells, compared to the billions in a human brain, said Ding Xue, co-author of the new research and professor in the (MCDB). But the neurons they do have work a lot like our own.听
鈥�C. elegans is probably the smallest animal that has all of the important cellular pathways that you find in humans,鈥� Xue said.
In their latest study, ,听the team designed a miniature facility called the 鈥淎coustic Gym,鈥� which is about the size of a quarter. The device uses sound waves to generate gentle whirlpools inside a reservoir of liquid, forcing C. elegans to swim against the current.
C. elegans worms seen under a microscope swimming inside an "Acoustic Gym." (Credit: Xiaoyun Ding)
"Gym-on-a-chip" with a liquid pool at the center. (Credit:听Xiaoyun Ding)
鈥淧reviously, the only way to study exercise in C. elegans was to, essentially, put them into a small container and shake it or let them swim as they wish,鈥� said study co-author Xiaoyun Ding, assistant professor in the Paul M. Rady Department of Mechanical Engineering. 鈥淲ith this new device, we can precisely control the intensity and duration of their swimming.鈥�
The researchers used the gym to examine the effect of exercise on a group of worms that lose neurons over time following a pattern similar to humans with Parkinson鈥檚鈥攁 neurologic disease in which people experience tremors and have trouble moving, among other symptoms. That degeneration, however, seemed to slow down in worms that swam for just the right amount of time.
鈥淭oo little or too much exercise doesn鈥檛 achieve the beneficial effect,鈥� Xue said. 鈥淭here鈥檚 a sweet spot.鈥�
Riding a bike
The biologist鈥檚 own interest in the brain and exercise dates back several years. Xue was watching the nightly news when he saw a story about a man with Parkinson鈥檚 disease whose symptoms improved when he went for a bike ride.听
鈥淎fter a bike ride, this patient suddenly became much more stable, and he was able to hold objects better,鈥� Xue said. 鈥淚 thought: 鈥楳aybe we could do something with that.鈥欌��
Studying exercise in real human patients, however, is not always easy. Many people with Parkinson鈥檚, for example, are older or can鈥檛 balance well enough to exercise consistently.听
The researcher, who has studied the cellular underpinnings of a wide variety of diseases, decided to turn to his old friend C. elegans.
Gym-on-a-chip
Xue and his team joined forces with Ding鈥檚 lab to create the perfect piece of exercise equipment for very small gym junkies. The researchers鈥� gym-on-a-chip includes a well that they can fill up with liquid and is the perfect size for C. elegans. Joyita Bhadra, a postdoctoral researcher in MCDB, and Nakul Sridhar, a graduate student in mechanical engineering, are co-lead authors of the new study.听
鈥淭he well is about 10 times larger than C. elegans,鈥� Ding said. 鈥淚t鈥檚 equivalent to how large a swimming pool is for humans.鈥�
In the study, the researchers dropped worms into these wells, then created slow waves that moved in a circle. The swimming exercises didn鈥檛 pose any harm to the worms, the team reports.
The researchers focused on two groups of C. elegans worms that scientists had genetically engineered to mimic human neurologic illnesses. One of these mutants, for example, has eight 鈥渄opaminergic鈥� neurons (cells that produce dopamine, an important molecule in the body and brain), which degrade and even die off over the animal鈥檚 lifetime. Parkinson鈥檚 disease affects the same kind of cells in human brains.
Exercise, however, could slow that loss.
With a little trial and error, the group discovered that swimming for just 5 minutes once a day for two days reduced the degradation of neurons in C. elegans by 28%, on average.
鈥淚f they only swim for 2 minutes, it doesn鈥檛 work,鈥� Xue said. 鈥淚f you force them to swim for 10 minutes, it doesn鈥檛 work.鈥�
Xue isn鈥檛 sure why exercise seems to help the worms. It may come down to the chemical biproducts that animals make when they flex their muscles. For now, the researchers want to use their gym-on-a-chip to start looking for new drugs that might be able to treat the symptoms of Parkinson鈥檚 disease鈥攁ll the benefits of exercise, without the exercise.
鈥淔or the first time, we have a platform to begin screening for drugs that could, for example, replace the beneficial effects of exercise,鈥� Xue said. 鈥淭hat could be really good for elderly people or others who aren鈥檛 able to exercise.鈥� 听
Co-authors of the new research include Apresio Kefin Fajrial, a graduate student in mechanical engineering at 精品SM在线影片, and MCDB undergraduate student Nia Hammond.
