2018 Fiscal Year Final Research Report
Development of novel mice models replicating Parkinson's disease pathology from its initial lesion
| Project/Area Number |
17K16119
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Keywords | パーキンソン病 / αシヌクレイン / 伝播 / マウスモデル |
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| Outline of Final Research Achievements |
The WT mice injected with α-Syn PFFs into the olfactory bulb (OB) showed sparse α-Syn pathology along the olfactory tract and in the hippocampus. Meanwhile, α-Syn BAC Tg mice injected with α-Syn PFFs into the OB displayed similar distribution of α-Syn pathology but drastic pathology. These mice manifested smell loss, anxiety in new environments, deficit of memory retention at 7-8 months post-injection, which are seen as non-motor symptoms of patients with Parkinson’s disease (article in preparation). The WT mice injected with α-Syn PFFs into the stomach developed α-Syn aggregates in the dorsal motor nucleus of vagus nerve (dmX), a finding that was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs. This suggests that the aggregates in the dmX were retrogradely induced via the vagal nerve (Uemura N et al., Mol Neurodegener 2018).
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| Free Research Field |
臨床神経学
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病（PD）のドパミン欠乏に基づく運動障害を主徴とする神経変性疾患で、病理学的特徴は神経細胞内αシヌクレイン凝集病変と黒質緻密部ドパミン神経細胞脱落である。しかし、αシヌクレイン凝集病変は脳内に広く観察され、また運動障害以外にも多様な非運動症状を呈する。これまで、多数の剖検解析から、αシヌクレイン凝集病変は嗅球と消化管神経叢から起こるとされるという仮説が提唱されていたが、これら最初期病変に由来する病理学的進展と症状発現については不明であった。本研究は、マウスの嗅球と消化管神経叢にαシヌクレインフィブリルを接種して解析することにより、PDの病態進行について新たな知見をもたらした。
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