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

Zhong, Chong Bin; Chen, Qian Qian; Haikal, Caroline LU ; Li, Wen LU ; Svanbergsson, Alexander LU ; Diepenbroek, Meike LU and Li, Jia Yi LU (2017) In Neuroscience Bulletin 33(5). p.483-492
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Enteric system, Parkinson’s disease, Phosphorylation, Protein aggregation, α-synuclein
in
Neuroscience Bulletin
volume
33
issue
5
pages
483 - 492
publisher
Science Press
external identifiers
  • scopus:85029582398
  • wos:000412740300002
ISSN
1673-7067
DOI
10.1007/s12264-017-0179-1
language
English
LU publication?
yes
id
5953b66f-1aa2-4075-9aa8-fe453812079f
date added to LUP
2017-09-29 10:58:37
date last changed
2018-01-31 15:27:44
@article{5953b66f-1aa2-4075-9aa8-fe453812079f,
  abstract     = {<p>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.</p>},
  author       = {Zhong, Chong Bin and Chen, Qian Qian and Haikal, Caroline and Li, Wen and Svanbergsson, Alexander and Diepenbroek, Meike and Li, Jia Yi},
  issn         = {1673-7067},
  keyword      = {Enteric system,Parkinson’s disease,Phosphorylation,Protein aggregation,α-synuclein},
  language     = {eng},
  month        = {09},
  number       = {5},
  pages        = {483--492},
  publisher    = {Science Press},
  series       = {Neuroscience Bulletin},
  title        = {Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson’s Disease},
  url          = {http://dx.doi.org/10.1007/s12264-017-0179-1},
  volume       = {33},
  year         = {2017},
}