Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson's disease
(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
- Chen, Qian Qian ; Haikal, Caroline LU ; Li, Wen LU ; Li, Ming Tao ; Wang, Zhan You and Li, Jia Yi LU
- organization
- publishing date
- 2018-06-30
- 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
- article number
- 13
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:29988485
- 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
- 2024-06-10 15:04:04
@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>}},
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}},
keywords = {{Calretinin; Colon; Enteric nervous system; NNOS; Parkinson's disease; Phosphorylation; VIP; α-syn}},
language = {{eng}},
month = {{06}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
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}},
doi = {{10.1186/s40035-018-0118-8}},
volume = {{7}},
year = {{2018}},
}