| First Author | McFleder RL | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 7529 |
| PubMed ID | 37981650 | Mgi Jnum | J:354471 |
| Mgi Id | MGI:7560895 | Doi | 10.1038/s41467-023-43224-z |
| Citation | McFleder RL, et al. (2023) Brain-to-gut trafficking of alpha-synuclein by CD11c(+) cells in a mouse model of Parkinson's disease. Nat Commun 14(1):7529 |
| abstractText | Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson's disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, alpha-synuclein (alphaSyn). Understanding the mechanism of propagation of alphaSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate alphaSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal alphaSyn aggregations are contained within CD11c(+) cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c(+) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c(+) cells traffic from the brain to the ileum. Together these data provide a mechanism of alphaSyn trafficking between the brain and gut. |
