The enteric nervous system （ENS） controls the function of the gastrointestinal tract and has been impli- cated in various diseases, including Parkinson＇s disease （PD）. PD is a neurodegenerative disease with Lewy ...The enteric nervous system （ENS） controls the function of the gastrointestinal tract and has been impli- cated 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 mor- phological 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 patho- logical 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.展开更多
基金supported by the National Natural Science Foundation of China (81430025)Northeastern University, China, as well as the Swedish Research Council (K201561X-22297-03-4)+5 种基金the EU Joint Programme-Neurodegenerative Disease Research (aSyn Protec and REfre AME),EU H2020-MSCAITN-2016 (Syndegen)Basal Ganglia Disorders Linnaeus Consortium-Excellence in Parkinson and Huntington Researchthe Strong Research Environment Multi Park (Multidisciplinary Research on Parkinson's disease)the Swedish Parkinson Foundation (Parkinsonfonden)the Torsten Sderbergs Foundation, and the Olle Engkvist Byggmstere Foundationsupported by a scholarship from the China Scholarship Council
文摘The enteric nervous system （ENS） controls the function of the gastrointestinal tract and has been impli- cated 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 mor- phological 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 patho- logical 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.
