45 years on: How serotonin makes schistosome parasites move

Jan 16, 2014
This is the expression of a serotonin receptor (bright green) in the Schistosoma mansoni nervous system. The muscles of the oral sucker and the muscular lining of the digestive tract appear in red. Credit: Nidhi Sharma, Institute of Parasitology, McGill University

Schistosoma mansoni and its close relatives are parasitic flatworms that affect millions worldwide and kill an estimated 250,000 people a year. A study published on January 16 in PLOS Pathogens identifies a new part of the molecular pathway that controls parasite movement. And because coordinated movement is essential for the schistosome life cycle in its human host, this protein is a promising new drug target.

"We know that many anti-parasitic drugs act on the worm's nervous system", says Paula Ribeiro from McGill University in Montreal, Canada, the lead author of the new study, "and have known for over 40 years that the neurotransmitter controls schistosome movement. As schistosomes are becoming resistant to the only effective drug we have, it was time to go after their ."

Serotonin is a signaling molecule that is used across species, including man, mouse, and worm. It exerts its function through specific serotonin receptors that span the membranes of . When these receptors pick-up serotonin the nerve cells become activated. In some cases, this activation in turn activates muscle cells, eventually resulting in movement.

As nobody had discovered a schistosome serotonin receptor yet, Ribeiro and colleagues started by a computer (or "in silico") search for DNA sequences from S. mansoni that looked similar to known serotonin receptor genes. They found a candidate and verified that the corresponding protein, which they called Schistosoma mansoni 5HTR, or Sm5HTR, is indeed a serotonin receptor. When cells that have the protein embedded in their membrane get exposed to serotonin on the outside, the scientists could measure a typical response inside these cells.

The scientists then went on to examine where in the parasite Sm5HTR is present, and report that the receptor is found widely on nerve cells in both larvae and adult worms. When they used various ways to interfere with , they found that larval and adult schistosomes were greatly inhibited in their movement. For example, when schistosome larvae are bathed in serotonin, they become twitchy and hyperactive. Larvae which have many fewer receptors don't show that response. And adult worms with fewer receptors move much less than those with normal numbers.

These studies suggest that even if schistosomes have additional serotonin receptors (and the in silico analysis suggests that there is at least one other), Sm5HTR is a major mediator of serotonin-controlled worm movement.

The authors conclude "We know from previous studies that locomotion is critical for survival of the parasite and that drug-induced paralysis is an effective way of clearing worm infections. Having identified Sm5HTR allows us to begin searching for selective receptor inhibitors that cause paralysis of the worm and may be suitable for therapeutic use."

Explore further: How JC Polyomavirus invades cells

More information: dx.plos.org/10.1371/journal.ppat.1003878

add to favorites email to friend print save as pdf

Related Stories

How JC Polyomavirus invades cells

Oct 07, 2013

For more than a decade the research group of Brown University Professor Walter Atwood has doggedly pursued the workings of the JC polyomavirus, which causes a disease called PML that fatally degrades the central nervous system ...

Ketamine acts as antidepressant by boosting serotonin

Jan 07, 2014

Ketamine is a potent anesthetic employed in human and veterinary medicine, and sometimes used illegally as a recreational drug. The drug is also a promising candidate for the fast treatment of depression in patients who do ...

In the brain, broken down 'motors' cause anxiety

Feb 07, 2013

When motors break down, getting where you want to go becomes a struggle. Problems arise in much the same way for critical brain receptors when the molecular motors they depend on fail to operate. Now, researchers reporting ...

Target for new Rx class for inflammatory disorders discovered

Oct 03, 2013

Research led by Charles Nichols, PhD, Associate Professor of Pharmacology at LSU Health Sciences Center New Orleans, describes a powerful new anti-inflammatory mechanism that could lead to the development of new oral medications ...

Stash of stem cells found in a human parasite

Feb 23, 2013

(Phys.org)—The parasites that cause schistosomiasis, one of the most common parasitic infections in the world, are notoriously long-lived. Researchers have now found stem cells inside the parasite that ...

Recommended for you

World's first microbe 'zoo' opens in Amsterdam

13 hours ago

The world's first "interactive microbe zoo" opened in Amsterdam on Tuesday, shining new light on the tiny creatures that make up two-thirds of all living matter and are vital for our planet's future.

Study shows how chimpanzees share skills

15 hours ago

Evidence of new behaviour being adopted and transmitted socially from one individual to another within a wild chimpanzee community is publishing on September 30 in the open access journal PLOS Biology. This i ...

Little blue penguin back at sea after hospital stint

20 hours ago

Wildbase Recovery Community Trust ambassador and Rangitikei MP Ian McKelvie joined Massey University veterinary staff to release a little blue penguin back into the sea at Himatangi Beach this morning.

User comments : 0