α-Synuclein spread from olfactory bulb causes hyposmia, anxiety, and memory loss in BAC-SNCA mice
| Autor: | Maiko T. Uemura, Masashi Ikuno, Ryosuke Takahashi, Masahide Asano, Norihito Uemura, Toru Yoshihara, Jun Ueda, Hodaka Yamakado, John Q. Trojanowski |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Olfactory system Postmortem studies Parkinson's disease Anosmia Hippocampus Mice Transgenic Anxiety Article 03 medical and health sciences Mice 0302 clinical medicine Limbic system Atrophy Hyposmia Medicine Animals Humans Memory Disorders business.industry medicine.disease Olfactory Bulb nervous system diseases Olfactory bulb Disease Models Animal 030104 developmental biology medicine.anatomical_structure nervous system Neurology alpha-Synuclein Neurology (clinical) medicine.symptom business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Mov Disord |
| Popis: | Background 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. Objective The objective of this study was to examine the clinicopathological contribution of α-Syn spread from the olfactory bulb. Methods 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. Results 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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