Abstract
Parkinson’s disease (PD) is pathologically characterized by intraneuronal α-synuclein (α-Syn) inclusions called Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Autopsy studies have suggested that Lewy pathology initially occurs in the olfactory bulb and enteric nervous system, subsequently spreading in the brain stereotypically. Recent studies have demonstrated that templated fibrillization and intercellular dissemination of misfolded α-Syn underlie this pathological progression. Injection of animals with α-Syn preformed fibrils (PFFs) can recapitulate LB-like inclusions and the subsequent intercellular transmission of α-Syn pathology. Moreover, targeting specific brain regions or body parts enables the generation of unique models depending on the injection sites. These features of α-Syn PFF-injected animal models provide a platform to explore disease mechanisms and to test disease modifying therapies in PD research. Here, we describe a methodology for the generation of α-Syn PFFs and the surgery on mice.
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Acknowledgments
This research is supported by the program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from Ministry of Education, Culture, Sports Science, MEXT, and the Japan Agency for Medical Research and Development, AMED under the Grant Number JP17dm0207020h0004 and JP20dm0207070 (RT), JSPS KAKENHI Grant Numbers JP17H05698 (RT), JP17K16119 (NU), the Takeda Science Foundation (NU), and the Kanae Foundation for the Promotion of Medical Science (NU).
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Uemura, N., Ueda, J., Okuda, S., Sawamura, M., Takahashi, R. (2021). α-Synuclein Propagation Mouse Models of Parkinson’s Disease. In: Imai, Y. (eds) Experimental Models of Parkinson’s Disease. Methods in Molecular Biology, vol 2322. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1495-2_12
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DOI: https://doi.org/10.1007/978-1-0716-1495-2_12
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