Making a gut-brain connection

This exercise is a part of Educator Guide: Parkinson’s Pathways / View Guide

These questions are based on the Science News article “Parkinson’s pathways.” Students should read the article introduction and answer related questions (Introduction to “Parkinson’s pathways”). Students can then form groups to read and answer questions about the sections of the article that you assign. The story sections are: Gut feeling, Neural highway, Belly bacteria, Microbial forces and Head for a cure. Note that Belly bacteria and Microbial forces should be assigned together. Once groups are finished, they can present the information they learned to the rest of the class. Finally, allow students to individually answer the final questions in the section titled, Summarize ideas and think critically.

Introduction to “Parkinson’s pathways”

1. What is Parkinson’s disease and what causes it?

Possible student response: Parkinson’s disease is a progressive, incurable disease in which nerve cells in a brain region involved in muscle control die. The cause of the disease is unknown, but abnormally clumped and misfolded proteins are the prime suspect. Some theories suggest that head trauma or exposure to environmental pollutants such as heavy metals, pesticides or air pollution might play a role.

2. Why are Parkinson’s researchers interested in the gut and nose?

Possible student response: People with Parkinson’s disease commonly lose their sense of smell and have digestive issues. Since the early 2000s, scientists have been gathering evidence that the malformed proteins in the brains of Parkinson’s patients might first appear in the gut or nose.

3. Describe a recent study that provides evidence for a link between the gut and Parkinson’s disease.

Possible student response: Scientists in Sweden reported that people who had their appendix removed had a lower risk of developing Parkinson’s disease years later. The appendix, attached to the colon, may play a role in intestinal health.

Gut feeling

4. Describe an early connection made between the gastrointestinal tract and Parkinson’s disease?

Possible student response: London physician James Parkinson, for whom Parkinson’s disease is named, wrote that some of his first patients with the disease had digestive problems. He treated two patients with a laxative and noted that their tremors subsided.

5. What is alpha-synuclein and what is known about its role in Parkinson’s disease?

Possible student response: In patients with Parkinson’s disease, the protein alpha-synuclein is abnormal and can become bundled with other proteins into Lewy bodies, which collect in the substantia nigra, a brain region that helps control movement.

6. What evidence did neuroanatomists Heiko Braak and Kelly Del Tredici and their collaborators find that suggested Parkinson’s might not arise in the brain?

Possible student response: The researchers tested for Lewy bodies and unbundled alpha-synuclein in deceased Parkinson’s patients. Based on comparisons with people without Parkinson’s, the team found signs that Lewy bodies had started to form in the nasal passages and intestines of Parkinson’s patients before showing up in the brain.

7. What is the standard treatment for Parkinson’s disease?

Possible student response: Parkinson’s disease kills nerve cells that produce the chemical messenger dopamine. Levodopa, a synthetic replacement for dopamine, can alleviate some symptoms. But the drug does not prevent the disease from progressing.

Neural highway

8. How might proteins associated with Parkinson’s disease travel from the gastrointestinal tract to the brain? What have experiments in mice found? 

Possible student response: Proteins might travel from the gut to the brain via the vagus nerve. In one study in mice, alpha-synuclein migrated from the intestine to the brain via the vagus nerve. In other studies, mice that ate and inhaled the pesticide rotenone developed Parkinson’s symptoms.

9. What results were found in patients who had their vagus nerve severed right above the stomach?

Possible student response: For people who had their vagus nerve cut, the risk of developing Parkinson’s began dropping five years after surgery, eventually reaching a difference of about 50 percent compared with people who had an intact vagus nerve.

10. What is LRKK2 and how does it relate to Parkinson’s disease and the gut?

Possible student response: LRKK2 is a gene involved in the immune system. Variations of the gene appear to increase the risk for developing inflammatory bowel disease and Parkinson’s.

11. What further links were found between inflammatory bowel disease and Parkinson’s disease?

Possible student response: In one analysis, patients with inflammatory bowel disease were about 30 percent more likely to develop Parkinson’s than people without the disease. And inflammatory bowel disease patients who took antitumor necrosis factor were 78 percent less likely to develop Parkinson’s than similar patients who did not take that drug.

Belly bacteria and Microbial forces

12. What results were found in mice that were genetically engineered to overproduce the alpha-synuclein protein?

Possible student response: If engineered mice were raised without any microorganisms in their insides, they did not develop Parkinson’s symptoms. If the mice were given microbes from healthy people, the mice developed some Parkinson’s symptoms. Mice given microbes from Parkinson’s patients developed severe Parkinson’s symptoms. The scientists suspect that something in the microbiome triggers the misfolding of alpha-synuclein.

13. What happened in one study when rats’ gut bacteria became stressed and produced their own amyloids? What does this suggest about a gut-brain connection?

Possible student response: When E. coli bacteria in rats’ intestines were stressed and produced amyloids — fibers of tightly stacked proteins — alpha-synuclein in the rats’ brains also formed amyloid clumps. The finding suggests that the immune system’s reaction to amyloid in the gut might somehow be involved in triggering amyloid formation in the brain.

Head for a cure

14. What do observational studies of Parkinson’s patients’ microbiomes find? What does the finding mean for our understanding of Parkinson’s disease?

Possible student response: Many Parkinson’s patients report serious gastrointestinal problems, and observational studies find differences in gut bacteria between Parkinson’s and non-Parkinson’s patients. But it’s too early to know how those differences might matter for the development of the disease.

15. How might microbiome research help Parkinson’s patients?

Possible student response: Doctors might be able to test for changes in the microbiome that put people at higher risk for developing Parkinson’s and restore healthy microbe populations through diet or some other means to delay or prevent the disease. Drugs may one day be developed that could stop the spread of abnormal alpha-synuclein from cell to cell.

16. Who is Martha Carlin and what is she doing to help promote further research of the microbiome and Parkinson’s?

Possible student response: Martha Carlin is a woman whose husband, John Carlin, was diagnosed with Parkinson’s disease. She founded a company that collects microbial samples from Parkinson’s patients for researchers to study.

17. Who is John Carlin and what is he doing to help people who are diagnosed with Parkinson’s?

Possible student response: John Carlin is a man who was diagnosed with Parkinson’s disease at age 44. He operates biking programs for people with Parkinson’s disease in order to stay active.

Summarize ideas and think critically

18. What is the central idea of the article?

Possible student response: Parkinson’s disease kills nerve cells that send signals from the brain to muscles, leading to uncontrolled movement. Recent evidence suggests that there might be a relationship between Parkinson’s and the gut, although the details are still not understood.

19. If the gut turns out to have an important role, what approaches could you imagine that might eventually treat Parkinson’s disease?

Possible student response: Detecting abnormal alpha-synuclein or other markers of Parkinson’s disease in the gastrointestinal tract or nose to potentially diagnose and begin treating Parkinson’s patients earlier. Using strong antibiotics to kill all of the potentially bad gut bacteria in Parkinson’s patients, then repopulating patients’ gastrointestinal tracts with bacteria from healthy people. Using drugs and/or surgery to stop potentially harmful proteins from moving from the gastrointestinal tract to the brain.

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