<scp>α</scp>‐Synuclein Spread from Olfactory Bulb Causes Hyposmia, Anxiety, and Memory Loss in <scp>BAC‐<i>SNCA</i></scp> Mice
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- Norihito Uemura
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
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- Jun Ueda
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
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- Toru Yoshihara
- Institute of Laboratory Animals, Graduate School of Medicine Kyoto University Kyoto Japan
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- Masashi Ikuno
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
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- Maiko T. Uemura
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
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- Hodaka Yamakado
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
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- Masahide Asano
- Institute of Laboratory Animals, Graduate School of Medicine Kyoto University Kyoto Japan
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- John Q. Trojanowski
- Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research University of Pennsylvania School of Medicine Philadelphia Pennsylvania USA
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- Ryosuke Takahashi
- Department of Neurology Kyoto University Graduate School of Medicine Kyoto Japan
書誌事項
- 公開日
- 2021-02-06
- 資源種別
- journal article
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1002/mds.28512
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Patients with Parkinson's disease (PD) show motor symptoms as well as various non‐motor symptoms. Postmortem studies of PD have suggested that initial alpha‐synuclein (α‐Syn) pathology develops independently in the olfactory bulb and lower brainstem, spreading from there stereotypically. However, it remains unclear how these two pathological pathways contribute to the clinicopathological progression of PD.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>The objective of this study was to examine the clinicopathological contribution of α‐Syn spread from the olfactory bulb.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted pathological and behavioral analyses of human α‐Syn bacterial artificial chromosome transgenic mice injected with α‐Syn preformed fibrils into the bilateral olfactory bulb up to 10 months postinjection.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>α‐Syn preformed fibril injections induced more widespread α‐Syn pathology in the transgenic mice than that in wild‐type mice. Severe α‐Syn pathology in the transgenic mice injected with α‐Syn preformed fibrils was initially observed along the olfactory pathway and later in the brain regions that are included in the limbic system and have connections with it. The α‐Syn pathology was accompanied by regional atrophy, neuron loss, reactive astrogliosis, and microglial activation, which were remarkable in the hippocampus. Behavioral analyses revealed hyposmia, followed by anxiety‐like behavior and memory impairment, but not motor dysfunction, depression‐like behavior, or circadian rhythm disturbance.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our data suggest that α‐Syn spread from the olfactory bulb mainly affects the olfactory pathway and limbic system as well as its related regions, leading to the development of hyposmia, anxiety, and memory loss in PD. © 2021 International Parkinson and Movement Disorder Society</jats:p></jats:sec>
収録刊行物
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- Movement Disorders
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Movement Disorders 36 (9), 2036-2047, 2021-02-06
Wiley
