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Geneticists create model for comprehending chronic stress

<p>Rutgers geneticists studied roundworms because of their simplicity. Roundworms have 300 neurons in their nervous system, while humans have about 100 billion neurons.</p>

Rutgers geneticists studied roundworms because of their simplicity. Roundworms have 300 neurons in their nervous system, while humans have about 100 billion neurons.

A team of Rutgers geneticists has created a new model for understanding chronic stress.

The study, published in the August issue of “Current Biology,” found the impact of chronic stress on the structure of six neurons in Caenorhabditis elegans roundworms, said Maureen Barr, a professor in the Department of Genetics.

Barr said the team studied roundworms because of their simplicity. They have 300 neurons in their nervous system, and in only three days hermaphroditic adults produce 300 offspring.

Meanwhile, she said the human nervous system has about 100 billion neurons.

“Humans have too many neurons for me to understand. Worms are a starting point,” Barr said.   

The worms are also transparent, so the team never had to cut them during the study, said Rebecca Androwski, a lab technician in Barr’s laboratory.

Androwski said the worms’ transparency drew her to the project. A recent graduate of the Mason Gross School of the Arts, Androwski entered Barr’s laboratory eager to work with cameras like those used in the team’s microscopes.

Because the worms are transparent, it was easy to take photographs of them, Androwski said.  They simply lit them with green fluorescent protein for easy viewing.

“I brought my interests in visual art and genetics together,” she said.

One of Androwski’s photographs of the worms appeared as the cover of the issue of “Current Biology” featuring the team’s article on study, she said.

The photograph depicts a worm’s neurons before it is stressed, while it is stressed and after it is stressed, Androwski said.

She said while starved and therefore stressed, the structure of the neurons became much more elaborate. Structural changes remained even after the starvation period ended.

“The effect is permanent,” said Alina Rashid, a School of Arts and Sciences junior working under Barr.

Normally, C. elegans have three stages of larval development before maturing. When stressed by starvation, overcrowding or heat, the worms enter an alternate stage instead of the normal third stage, Rashid said.

Rashid said in this alternate stage, known as the dauer stage, the worms combat stress. They shed skin over their mouths, do not eat and remain idle to conserve energy.

“The dauer worms are amazing,” Barr said. “They withstood the Space Shuttle Columbia crash in 2003.”

Barr said this stage is where the neuronal changes appeared.

The study is the first to show traumatic environmental impact on worms in the dauer stage, she said.

Rashid said the branching of the nervous system could compensate for other neurons. She has been testing the branching’s impact on movement and sense of touch.

“No one knows what the function of the branching truly is,” she said.  

Nathan Schroeder, a post-doctoral fellow formerly under Barr, said he determined how the branching occurs at a molecular level.

To study the change, Schroeder said he exposed wild-type, or normal, worms to mutagens that changed their DNA. He then looked at the branching of their mutated offspring’s neurons.

In the offspring, Schroeder said he observed several differences, including no branching, extra branching and disorganized branching.

With the team, Schroeder said he has already found the enzyme responsible for disorganized branching.

The enzyme, KPC-1, is also found in humans, Schroeder said. Known as furin, experiments in rodents have shown furin is essential in normal development.

If furin were the target of an anti-stress disorder drug, the drug could selectively inhibit its activity, Schroeder said.

Theoretically, he said if the research team identified the gene controlling furin, then they could stop its action.

“It’s much more complicated in humans,” he said.

While Schroeder studied the genes controlling the branching’s mechanism, Barr said they are now studying the worms’ nervous systems recovery from stress.

Once understood, Barr said the team’s research would help answer why some people respond to stress much better than others do.

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