Transneuronal Propagation of Pathologica-Synuclein from the Gut to the Brain Models Parkinson's disease (Neuron 2019, 103:1-15)

報告日期: 2019/11/29
報告時間: 16:00/16:50
報告學生: 劉嘉瑋
講評老師: 陳珮君
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Transneuronal Propagation of Pathologic -Synuclein from the Gut to the Brain Models Parkinson’s Disease

Kim et al., 2019, Neuron 103, 1–15

Speaker: Chia-Wei Liou;                          Commentator: Pei-Chun Chen, Ph.D.

Parkinson’s disease (PD) is a neurodegenerative disorder and characterized by tremor, bradykinesia, and rigidity. Loss of dopaminergic neurons in the substantial nigra pars compacta (SNc) caused by aggregation of a-synucleins, which serves as the hallmarks of PD. Previous clinical studies demonstrated that the pathologic -synucleins have been observed in the central nervous system, enteric nerves system and gastrointestinal (GI) tract in patients with PD [1, 2]. So, they hypothesized that -synucleins spread from the gut to brain via the vagus nerve that enables the bidirectional connection between the brain and the GI tract. Mice were injected with -synuclein preformed fibrils into the upper duodenum and pyloric stomach followed by detailed exminaiton of dorsal motor nucleus and the hindbrain using the antibody against phosphorylated a synuclein at serine 129. Pathologic -synucleins have been firstly found in the dorsal motor nucleus and much later in locus coeruleus, basolateral amygdala, and SNc as well as the olfactory bulb which corresponds to the Braak hypothesis.Besides, gut-injected -synucleins in mice shows pathologies of PD, including loss of dopaminergic neuron in the SNc, motor dysfunctions, and cognitive deficits. Importantly, truncal vagotomy and knockout of Snca prevent the PD-like pathologies caused by gut-injected a-synucleins. Collectively, this study provides temporal and stereotypical spreading of Lewy Body pathology from gut to brain, leading to clinical features including motor and non-motor symptoms and highlights the importance of the gut-brain axis in the etiology of PD.

Keywords
Parkinson’s disease, -synuclein, vagus nerve, gut-brain axis

Reference

  1. Braak, H., et al., Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging, 2003. 24(2): p. 197-211.
  2. Chandra, R., et al., alpha-Synuclein in gut endocrine cells and its implications for Parkinson's disease. JCI Insight, 2017. 2(12).