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

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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; Li, Wen; Svanbergsson, Alexander; Diepenbroek, Meike; Li, Jia Yi.

I: Neuroscience Bulletin, Vol. 33, Nr. 5, 2017, s. 483-492.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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T1 - Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson’s Disease

AU - Zhong, Chong Bin

AU - Chen, Qian Qian

AU - Haikal, Caroline

AU - Li, Wen

AU - Svanbergsson, Alexander

AU - Diepenbroek, Meike

AU - Li, Jia Yi

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Enteric system

KW - Parkinson’s disease

KW - Phosphorylation

KW - Protein aggregation

KW - α-synuclein

U2 - 10.1007/s12264-017-0179-1

DO - 10.1007/s12264-017-0179-1

M3 - Article

VL - 33

SP - 483

EP - 492

JO - Neuroscience Bulletin

T2 - Neuroscience Bulletin

JF - Neuroscience Bulletin

SN - 1673-7067

IS - 5

ER -