Data from: Gut mucosal cells transfer α-synuclein to the vagus nerve

• Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to brain and increase the risk of Parkinson’s disease (PD). While past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut to brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of intestinal mucosa express α-synuclein. Here, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from epithelial cells in organoids to cocultured nodose neurons devoid of α-synuclein. In mice expressing human α-synuclein, but no mouse α-synuclein, α-synuclein fibril templating activity emerges in α-synuclein seeded fibril aggregation assays in intestine, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfers to the vagus nerve and dorsal motor nucleus. Subdiaphragmatic vagotomy prior to induction of α-synuclein expression in intestinal epithelial cells effectively protects the hindbrain from emergence of α-synuclein fibril templating activity. Overall, these findings highlight a potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells. ... [Read More]

Total Size

2 files (122 KB)

Data Citation

• Chandra, R., Sokratian A., Chavez K. R., King S., Swain S. M., Snyder J. C., West A. B., & Liddle R. A. (2023). Data from: Gut mucosal cells transfer α-synuclein to the vagus nerve. Duke Research Data Repository. https://doi.org/10.7924/r4542x03c

Creator

• King, Stephanie
• Liddle, Rodger A.
• West, Andrew B.
• Swain, Sandip M.
• Sokratian, Arpine
• Snyder, Joshua C.
• Chandra, Rashmi
• Chavez, Katherine R.

DOI

• 10.7924/r4542x03c

Subject

• Brain-Gut Axis
• Prions
• Mouse model
• Real time quaking-induced conversion (RT-QuIC)
• SNCAbow
• Parkinson Disease

Publication Date

• October 24, 2023

ARK

• ark:/87924/r4542x03c

Contributor

• Karuppagounder, Senthil

Affiliation

• Aligning Science Across Parkinson's (ASAP) Collaborative Research Network
• Surgery
• Pharmacology & Cancer Biology
• Medicine
• Cell Biology
• Duke Institute for Brain Sciences
• Department of Veterans Affairs

Publisher

• Duke Research Data Repository

Language

• English

Type

• Dataset

Format

• XLSX

Related Materials

• Chandra, R., Sokratian, A., Chavez, K. R., King, S., Swain, S. M., Snyder, J. C., West, A. B., & Liddle, R. A. (2023). Gut mucosal cells transfer α-synuclein to the vagus nerve. JCI insight, 8(23), e172192.  https://doi.org/10.1172/jci.insight.172192

Contact

• Rodger Liddle, 919-681-6380, https://orcid.org/0000-0002-5498-4151.

License

• Creative Commons CC0 1.0 Universal

Title

• Data from: Gut mucosal cells transfer α-synuclein to the vagus nerve

License

• http://creativecommons.org/publicdomain/zero/1.0/

Repository

• Duke Research Data Repository