Brain-to-gut trafficking of alpha-synuclein by CD11c + cells in a mouse model of Parkinson's disease.
Rhonda L McFlederAnastasiia MakhotkinaJanos GrohUrsula KeberFabian ImdahlJosefina Peña MoscaAlina PeteranderlJingjing WuSawako TabuchiJan HoffmannAnn-Kathrin KarlAxel PagenstecherJörg VogelAndreas BeilhackJames B KoprichJonathan M BrotchieAntoine-Emmanuel SalibaJens VolkmannChi Wang IpPublished in: Nature communications (2023)
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, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn 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 αSyn trafficking between the brain and gut.
Keyphrases
- induced apoptosis
- resting state
- white matter
- cell cycle arrest
- single cell
- mouse model
- functional connectivity
- oxidative stress
- cerebral ischemia
- cell death
- type diabetes
- adipose tissue
- spinal cord
- metabolic syndrome
- cell proliferation
- blood brain barrier
- high fat diet induced
- nk cells
- insulin resistance
- protein protein