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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

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Abstract

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.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81430025) and Northeastern University, China, as well as the Swedish Research Council (K2015-61X-22297-03-4), the EU Joint Programme—Neurodegenerative Disease Research (aSynProtec and REfreAME), EU H2020-MSCA-ITN-2016 (Syndegen), Basal Ganglia Disorders Linnaeus Consortium-Excellence in Parkinson and Huntington Research, the Strong Research Environment MultiPark (Multidisciplinary Research on Parkinson’s disease), the Swedish Parkinson Foundation (Parkinsonfonden), the Torsten Söderbergs Foundation, and the Olle Engkvist Byggmästere Foundation. W. L. is supported by a scholarship from the China Scholarship Council.

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Authors and Affiliations

  1. Institute of Bioengineering, Northeastern University, Shenyang, 110819, China

    Chong-Bin Zhong & Qian-Qian Chen

  2. Institute of Neuroscience, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China

    Qian-Qian Chen & Jia-Yi Li

  3. Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, BMC A10, 22184, Lund, Sweden

    Caroline Haikal, Wen Li, Alexander Svanbergsson, Meike Diepenbroek & Jia-Yi Li

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  1. Chong-Bin Zhong
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  4. Wen Li
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Correspondence to Jia-Yi Li.

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Zhong, CB., Chen, QQ., Haikal, C. et al. Age-Dependent Alpha-Synuclein Accumulation and Phosphorylation in the Enteric Nervous System in a Transgenic Mouse Model of Parkinson’s Disease. Neurosci. Bull. 33, 483–492 (2017). https://doi.org/10.1007/s12264-017-0179-1

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  • DOI: https://doi.org/10.1007/s12264-017-0179-1

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