Post-Traumatic Stress Disorder

How Roundworms Could Help PTSD Sufferers

Optogenetics shines a light on the physiology of associative memories.

Posted May 02, 2019

RUANSHUNYI/Pixabay
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Source: RUANSHUNYI/Pixabay

During their lifetime, many people will encounter highly traumatic events, however only a fraction goes on to develop symptoms that persist for over month, and possibly even years—post-traumatic stress disorder (PTSD), a mental health disorder that impacts approximately 7.7 million Americans, roughly 3.5 percent of the U.S. adults population, according to the Anxiety and Depression Association of American. The reason why is not yet fully understood. A new scientific study published today in Current Biology by Hebrew University of Jerusalem’s researchers provides insight into the physiology of PTSD by examining the neurons involved in the memory circuit of roundworms.

Why use roundworms to better understand PTSD in humans? According to the researchers, “As learning and memory abilities are presumably universal across the animal kingdom, it is appealing to study such paradigms within animals with a compact nervous system where individual target neurons can be identified and tracked.”

The type of roundworm used in the study, Caenorhabditis elegans (C. elegans), was the first multicellular organism to have its whole genome sequenced according to the National Human Genome Research Institute. Approximately 40 percent of its 20,000 genes are similar to human genes.

The team wrote, “C. elegans nematodes offer a unique opportunity, as the wiring of their neural system, consisted of 302 neurons, has been fully mapped.” They added that these roundworms “exhibit a range of learning and memory abilities, including associative memory, which can be studied at a single-neuron resolution.”

Additionally, a link between genetics and PTSD has been established previously by a different research team two years ago. In 2017, the first molecular evidence of the genetic influences on the development of PTSD was demonstrated. The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) published a research study in Molecular Psychiatry on April 25, 2017 with senior author Karestan Koenen of Harvard T. H. Chan School of Public Health, and the Broad Institute of MIT and Harvard, that showed that those with higher genetic risk for several mental health disorders such as schizophrenia are also at higher genetic risk for PTSD—establishing some genetic overlap.

Dr. Alon Zaslaver, research associate Dr. Yifat Eliezer, and others from the Department of Genetics at The Hebrew University of Jerusalem trained the roundworms to form associative memories through a process of starving, then spraying them with a scent. The researchers aimed to have the roundworms associate the scent with extreme hunger, a highly stressful event.

After a day of withholding food, the team fed the roundworms and sprayed them again with the same scent. The researchers observed the roundworms activating the genes for stress-protection.

The team used neuro-genetic techniques to “pinpoint the exact neurons that hold associative memories” in the roundworms. Once the team identified the neurons for associated memory of roundworms, they genetically engineered a different set of roundworms in a manner that its stress-response could be switched on by light.

Specifically, the team performed optogenetics by inserting the pinpointed neurons with channelrhodopsin-2 (ChR2), a light-sensitive protein (opsin) from green algae Chlamydomonas reinhardtii. Neurons inserted with ChR2 switch on when exposed to blue light, and turn off when the light is off. By using optogenetics, the researchers discovered that this new set of roundworms retained the memories of starvation, and showed a stress reaction when the neurons were light-activated without using scent.

PTSD can be treated by either psychotherapy or pharmaceuticals, or a combination of the two approaches. Zaslaver and the research team plans to apply their discovery towards finding ways of relieving, and perhaps even one day curing the specific triggers that cause PTSD. Understanding who might be vulnerable to PTSD at a molecular level may help identify therapeutic targets that lead to innovative treatments in the future.

Copyright © 2019 Cami Rosso All rights reserved.

References

Eliezer, Yifat, Deshe, Noa, Hoch, Lihi, Iwanir, Shachar, Pritz, Christian O., Zaslaver, Alon. “A Memory Circuit for Coping with Impending Adversity.” Current Biology. May 2, 2019.

Hebrew University of Jerusalem. “Make room on the couch: Worms suffer from PTSD, too.” Phys.org. May 2, 2019.

John G White, Eileen Southgate, J Nichol Thomson, Sydney Brenner. “The structure of the nervous system of the nematode Caenorhabditis elegans.” Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. Nov. 12, 1986.

Anxiety and Depression Association of American. “Facts and Statistics.” Retrieved 5-2-2019 from https://adaa.org/about-adaa/press-room/facts-statistics

NIH. “1998: Genome of Roundworm C. elegans Sequenced.” Retrieved 5-2-2019 from https://www.genome.gov/25520394/online-education-kit-1998-genome-of-roundworm-c-elegans-sequenced

Harvard T.H. Chan School of Public Health (2017, April 25). Study finds first molecular genetic evidence of PTSD heritability [Press Release]. Retrieved from https://www.hsph.harvard.edu/news/press-releases/molecular-genetic-evidence-ptsd-heritability/