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Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson's disease

Chen, Qian Qian; Haikal, Caroline LU ; Li, Wen LU ; Li, Ming Tao; Wang, Zhan You and Li, Jia Yi LU (2018) In Translational Neurodegeneration 7(1).
Abstract

Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods: In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter. Results: We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons... (More)

Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods: In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter. Results: We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner's (submucosal) and Auerbach's (myenteric) plexuses of the colon. Additionally, the phosphorylation of α-syn at serine 129 also increased with age and the aggregation of α-syn-GFP coincided with the appearance of motor deficits at 9 months of age. Furthermore, α-syn (-GFP) distinctly co-localized with different subtypes of neurons, as identified by immunohistochemical labeling of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin. Conclusions: Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Calretinin, Colon, Enteric nervous system, NNOS, Parkinson's disease, Phosphorylation, VIP, α-syn
in
Translational Neurodegeneration
volume
7
issue
1
external identifiers
  • scopus:85049260962
ISSN
2047-9158
DOI
10.1186/s40035-018-0118-8
language
English
LU publication?
yes
id
b09a77b8-1a05-468e-bc07-4e1a1b7d6eca
date added to LUP
2018-07-13 13:37:37
date last changed
2018-07-14 03:00:04
@article{b09a77b8-1a05-468e-bc07-4e1a1b7d6eca,
  abstract     = {<p>Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods: In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter. Results: We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner's (submucosal) and Auerbach's (myenteric) plexuses of the colon. Additionally, the phosphorylation of α-syn at serine 129 also increased with age and the aggregation of α-syn-GFP coincided with the appearance of motor deficits at 9 months of age. Furthermore, α-syn (-GFP) distinctly co-localized with different subtypes of neurons, as identified by immunohistochemical labeling of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin. Conclusions: Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.</p>},
  articleno    = {13},
  author       = {Chen, Qian Qian and Haikal, Caroline and Li, Wen and Li, Ming Tao and Wang, Zhan You and Li, Jia Yi},
  issn         = {2047-9158},
  keyword      = {Calretinin,Colon,Enteric nervous system,NNOS,Parkinson's disease,Phosphorylation,VIP,α-syn},
  language     = {eng},
  month        = {06},
  number       = {1},
  series       = {Translational Neurodegeneration},
  title        = {Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson's disease},
  url          = {http://dx.doi.org/10.1186/s40035-018-0118-8},
  volume       = {7},
  year         = {2018},
}