ORIGINAL RESEARCH article
Front. Cell. Neurosci.
Sec. Non-Neuronal Cells
Volume 19 - 2025 | doi: 10.3389/fncel.2025.1624593
This article is part of the Research TopicCellular and Animal Models of Neurodegenerative and Neuroinflammatory ConditionsView all articles
Rotenone accelerates endogenous α-synuclein spreading and enhances neurodegeneration in an intra-striatal α-synuclein preformed fibril (PFF) injected mouse model of Parkinson's Disease
Provisionally accepted
- 1United Arab Emirates University, Al-Ain, United Arab Emirates
- 2Al-Ahliyya Amman University, Amman, Jordan, Amman, Jordan
- 3Parkinson Clinic and Research, Kamakura, Japan
- 4Parkinson Clinic and Research, Kamakura 247-0061, Japan
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Prominent histopathological features of Parkinson's disease (PD) include the presence of Lewy bodies, intra-neural protein aggregates mainly composed of α-synuclein (α-syn), and cell death of dopaminergic neurons. Epidemiological studies have revealed a correlation between exposure to environmental neurotoxins, such as rotenone, and an increased risk of developing PD. In this study, we evaluated the role of rotenone in α-syn spreading and accumulation, with the aim of developing a mouse model of accelerated PD. Human α-synuclein pre-formed fibrils (PFF) were injected into the mouse striatum by stereotactic surgery. Rotenone (2.5mg/kg-body-weight) was administered intraperitoneally once daily for four consecutive weeks one day or three weeks after the PFF injection. Brains were collected twenty-four hours after the last injection for immunohistochemical analysis. In this study, Rotenone significantly synergized PFF induced α-syn spreading, neuroinflammation, in addition to augmented loss of dopaminergic neurons along the nigrostriatal pathway.
Keywords: α-Synuclein, mouse model, neurodegeneration, Parkinson's disease, Rotenone
Received: 07 May 2025; Accepted: 05 Sep 2025.
Copyright: © 2025 Khan, Radwan, Ardah, Kitada and Haque. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: M Emdadul Haque, ehaque@uaeu.ac.ae
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