TY  - JOUR
AB  - Background: In some people with Parkinson’s disease (PD), a-synuclein (αSyn) accumulation may begin in the enteric nervous system (ENS) decades before development of brain pathology and disease diagnosis.
Objective: To determine how different types and severity of intestinal inflammation could trigger αSyn accumulation in the ENS and the subsequent development of αSyn brain pathology.
Methods: We assessed the effects of modulating short- and long-term experimental colitis on αSyn accumulation in the gut of αSyn transgenic and wild type mice by immunostaining and gene expression analysis. To determine the long-term effect on the brain, we induced dextran sulfate sodium (DSS) colitis in young αSyn transgenic mice and aged them under normal conditions up to 9 or 21 months before tissue analyses.
Results: A single strong or sustained mild DSS colitis triggered αSyn accumulation in the submucosal plexus of wild type and αSyn transgenic mice, while short-term mild DSS colitis or inflammation induced by lipopolysaccharide did not have such an effect. Genetic and pharmacological modulation of macrophage-associated pathways modulated the severity of enteric αSyn. Remarkably, experimental colitis at three months of age exacerbated the accumulation of aggregated phospho-Serine 129 αSyn in the midbrain (including the substantia nigra), in 21- but not 9-month-old αSyn transgenic mice. This increase in midbrain αSyn accumulation is accompanied by the loss of tyrosine hydroxylase-immunoreactive nigral neurons.
Conclusions: Our data suggest that specific types and severity of intestinal inflammation, mediated by monocyte/macrophage signaling, could play a critical role in the initiation and progression of PD.
DA  - 2021-05-18
DO  - 10.17879/freeneuropathology-2021-3326
LA  - eng
PY  - 2021-05-18
SN  - 2699-4445
T2  - Free Neuropathology
TI  - Specific immune modulation of experimental colitis drives enteric alpha-synuclein accumulation and triggers age-related Parkinson-like brain pathology
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6:3-freeneuropathology-2021-33358
Y2  - 2024-11-22T16:16:38
ER  -