‘Worm spitting’ offers insights for heart research

27 Jul

At first sight, it may not look like we have much in common with the nematode Caenorhabditis

elegans, a bacteria-chomping roundworm that is typically found in soil. But take a closer look,

and it becomes clear why this little creature is so loved by biologists studying the nature of

cells.

electron microscope view of C elegans
This 3D reconstruction of the pharynx of the C. elegans nematode shows the location of the M1 neuron – in the center – that controls the worm’s spitting behavior.
Image credit: Nikhil Bhatla et al., MIT

For instance, C. elegans is multicellular and develops from a fertilized egg, just like

we do, and its cells have features in common with some of our cells. And now, a new study reveals

it tastes and spits out toxic food – a survival mechanism it shares with many complex organisms.

The scientists behind the new study discovered that the way the worm uses its pharynx – the

front part of its feeding tube – to spit out nasty, toxic food, could have important implications

for human heart research.

In the simple worm, the pharynx is essentially a myogenic muscular pump that rhythmically sucks

bacteria into its intestine. The muscle of the simple organ is made of myogenic cells that contract

without nervous system stimulation – like myogenic muscle in the human heart and other organs.

In the journal Current Biology, researchers from the Massachusetts Institute of

Technology (MIT) in Cambridge, MA, report how they identified three circuits that control the

worm’s feeding organ.

Worm’s spitting behavior ‘reminiscent of heart valvular diseases’

Two of the circuits the team identified are inside the worm’s feeding organ – one stops the

feeding pump while the other triggers spitting. The third circuit relays signals from outside the

organ, not unlike the autonomic nervous system that helps control internal organs in more complex

organisms.

The team says finding out how nerve cells control the pharynx in C. elegans could help

us better understand human myogenic muscles – such as those in the heart and the stomach.

For

example, the human heart has cells that contract on their own without external stimulus to pump

substances through tubes. It also relies on external signals from the brain, to regulate heart

rate and other functions.

First author Dr. Nikhil Bhatla, a biologist at MIT, says the findings also raise other points of

interest. The worm’s spitting behavior makes them think of valvular heart diseases,

where blood is sometimes pumped in the wrong direction. He says this raises the question:

“Are there neurons in the heart that are detecting the levels of oxygen, or certain

hormones, or other molecules, and controlling when the valves open and close?”

In previous work, the team had discovered that in several of the worm’s nerve cells two taste

receptors – GUR-3 and LITE-1 – control the worm’s response to toxins such as hydrogen peroxide and

other harmful reactive oxygen compounds that violet and ultraviolet light can produce.

They noticed that when the worm “tastes” these compounds it stops feeding and moves away from

the light.

Study shows the worm is spitting, not regurgitating

In the new study, the team observed what happened when they shone the light for longer. They

noticed this triggered a “burst response” where the worm would initially stop feeding, then start

again, in short bursts of stop-start activity.

When they took a closer look at the worm’s feeding burst responses, the team noticed bubbles

appearing around the worm’s mouth – like spit.

Closer examination with a 1,000-frame-per-second camera attached to the microscope revealed that

the spit bubbles contained ingested bacteria. There is evidence of other nematodes “spitting,” but

for different reasons. For example, some parasitic worms regurgitate – they spit substances into

plants to turn them into liquids for digestion.

“But no one knew the simple C. elegans worm could spit,” comments Dr. Bhatla.

“It was completely unexpected.”

They already knew that the worm can push out liquids through its mouth – it filters and expels

unneeded fluids while retaining the bacteria it feeds on. But the team says it looks like the worm

does not close its filter when it tastes toxic chemicals – it just expels the whole lot.

One of the many reasons biologists use C. elegans to study cell and tissue behavior is

because – unlike humans who have billions of neurons – the worm only has 302 nerve cells. This has

allowed all the connections be mapped – revealing what scientists call the worm’s “connectome.”

Findings could lead to new remedies for heart valvular diseases

For the study, the team identified the neurons that control the worm’s food intake by gradually

killing the 20 neurons in the pharynx. They found when they killed a neuron known as M1, the worm

stopped spitting. The neuron expresses the LITE-1 taste receptor.

The researchers believe the discovery could help us better understand heart conditions.

For instance, it may reveal a new cause of aortic regurgitation, where – due to imperfect closing of heart valves – oxygenated blood flows

backward into the heart instead of out into the rest of the body.

Dr. Bhatla says that if they find the human heart also contains M1-like neurons then perhaps they are sensing harmful substances in the blood and telling the heart

valves to stay open – possibly to stop the substances spreading.

The researchers note in their paper:

“If this analogy is confirmed, novel therapeutics might provide an alternative to

surgery to remedy valvular heart disease by inhibiting the function of such

neurons.”

The National Institutes of Health funded the study.

Last month, Medical News Today learned how nematode worms played an important part in a

study that raises new treatment hope for amyotrophic lateral

sclerosis or ALS. The study team says their work could lead to new ways of developing drugs for a whole range of

neurodegenerative disorders such as ALS, Alzheimer’s, Parkinson’s and Huntington’s diseases.

Written by Catharine Paddock PhD

Copyright: Medical News Today


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