Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson's Disease

Neurosci Bull. 2017 Oct;33(5):483-492. doi: 10.1007/s12264-017-0179-1. Epub 2017 Sep 18.


The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model. We found that the expression and accumulation of α-syn increased gradually in neurons of Meissner's and Auerbach's plexuses of the gastrointestinal tract with age (from 1 week to 2 years). In addition, α-syn was increasingly phosphorylated at the serine 129 residue, reflecting pathological alterations of the protein over time. Furthermore, α-syn was present in different subtypes of neurons expressing vasoactive intestinal polypeptide, neuronal nitric oxide synthase, or calretinin. The results indicated that BAC-α-Syn-GFP transgenic mice provide a unique model in which to study the relationship between ENS and PD pathogenesis.

Keywords: Enteric system; Parkinson’s disease; Phosphorylation; Protein aggregation; α-synuclein.

MeSH terms

  • Age Factors
  • Animals
  • Disease Models, Animal*
  • Enteric Nervous System / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism
  • Parkinson Disease / metabolism*
  • Phosphorylation
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • Snca protein, mouse
  • alpha-Synuclein