Aggregation of alpha-synuclein in enteric neurons does not impact function in vitro.

Recent evidence implicates a gut-first pathogenesis in the enteric nervous system (ENS) within a portion of PD patients, yet in vitro investigations have primarily focused on the central nervous system. Here, the preformed fibril (PFF) PD model is applied with co-administered groups of butyrate and lipopolysaccharide to model the effects of the local gut microbiome. Significant PFF uptake and retention occur in isolated rat enteric neurons compared to untreated controls resulting in increasing immunostained aggregate conformation-specific, alpha-synuclein (a-Syn) average intensity between 6 µg PFF and untreated controls.

These organoids have some nerve: Uniting three germ layers in a human gastric model system.

Gastrointestinal organoids provide an accessible model for studying human development and disease. In this issue of Cell Stem Cell, Eicher et al. (2022) direct human pluripotent stem cells to incorporate three germ layers into gastric organoids, recapitulating the structure and function of human gut tissue in an in vitro model.