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

• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2017,（5）
• 页码范围: 483-492
• 页数: 10页
• 语种: 英文
• DOI: 10.1007/s12264-017-0179-1

摘要

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.