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

Tabular raw data corresponding to figure sets used in the study. 

Figure 1. α-Synuclein expression and seeding activity in SNCAA53T mice. ELISA quantification of human α-synuclein in (C) duodenum (α-synuclein quantification in ng/mg of nodose tissue), (D) nodose ganglia (α-synuclein quantification in pg/mg of nodose tissue), and (E) hindbrain (α-synuclein quantification in ng/mg of nodose tissue), from Snca–/– and SNCAA53T mice. RT-QuIC analysis of (F) duodenum, (G) nodose ganglia, and (H) hindbrain of Snca–/– and SNCAA53T mice. 

Figure 3. Conditional human α-synuclein expression induces α-synuclein seeding activity in gut organoids. (C) A representative ThT fluorescence profile for these genotypes is provided. (D) Endpoint values were collected after 100 hours of RT-QuIC relative to negative controls.

Figure 4. Conditional human α-synuclein expression in gut mucosal cells produces in α-synuclein seeding activity in nodose ganglia. (C) ELISA quantification of human α-synuclein protein in nodose ganglia of nontransgenic, Snca–/–, and SNCAbow mice. (D) A representative ThT fluorescence profile (RT-QuIC) and endpoint analysis of nodose ganglia from nontransgenic (nTg), Snca–/–, and SNCAbow mice at 1 month of age. (E) RT-QuIC analysis of nodose ganglia from 6-month-old nTg, Snca–/–, and SNCAbow mice.

Figure 5. Vagotomy spares the nodose ganglia from α-synuclein seeding activity and prevents spread to the hindbrain. (C) ELISA measurements of α-synuclein protein in the gut 3 months after tamoxifen treatment. RT-QuIC analysis of (D and E) vagal nodose ganglia and (F and G) hindbrain analyzed 3 months after tamoxifen treatment. Representative ThT fluorescence profiles are shown in D and F.

Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease. Although 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 emerged 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 transfered to the vagus nerve and dorsal motor nucleus. Subdiaphragmatic vagotomy prior to induction of α-synuclein expression in intestinal epithelial cells effectively protected 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.