DOI: 10.1101/505164Dec 22, 2018Paper

Experimental colitis drives enteric alpha-synuclein accumulation and Parkinson-like brain pathology

BioRxiv : the Preprint Server for Biology
Stefan GrathwhohlMarkus Britschgi

Abstract

Intraneuronal α-synuclein accumulation is key in Parkinson's disease (PD) pathogenesis. The pathogenic process is suggested to begin in the enteric nervous system and propagate into the brain already decades before diagnosis of PD. In some patients, colitis might play a critical role in this process. Here we demonstrate that patients with inflammatory bowel disease exhibit α-synuclein accumulation in the colon and that experimental colitis triggers α-synuclein accumulation in certain enteric nerves of mice. The type and degree of experimental inflammation modulates the extent of colonic α-synuclein accumulation and macrophage-related signaling limits this process. Remarkably, experimental colitis at three months of age exacerbates the accumulation of aggregated phospho-Serine 129 α-synuclein in the midbrain (including the substantia nigra), in 21- but not 9-month-old α-synuclein transgenic mice. This is accompanied by loss of tyrosine hydroxylase-immunoreactive nigral neurons. Our data suggest that intestinal inflammation might play a critical role in the initiation and progression of PD.

Related Concepts

Brain
Brain Pathology
Colitis
Colon Structure (Body Structure)
Inflammation
Inflammatory Bowel Diseases
Macrophage Activation
Midbrain Structure
Laboratory mice
Mice, Transgenic

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