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Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4‐phenylbutyrate, a chemical chaperone

Inden, Masatoshi, Kitamura, Yoshihisa, Takeuchi, Hiroki, Yanagida, Takashi, Takata, Kazuyuki, Kobayashi, Yuka, Taniguchi, Takashi, Yoshimoto, Kanji, Kaneko, Masahiko, Okuma, Yasunobu, Taira, Takahiro, Ariga, Hiroyoshi, Shimohama, Shun·2007·Journal of Neurochemistry

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Previous studies have demonstrated that chronic systemic exposure of Lewis rats to rotenone produced many features of PD, and cerebral tauopathy was also detected in the case of severe weight loss. The present study was designed to assess the neurotoxicity of rotenone after daily oral administration for 28 days at several doses in C57BL/6 mice. In addition, we examined the protective effects of 4‐phenylbutyrate (4‐PBA) on nigral dopamine (DA) neurons in rotenone‐treated mice. 4‐PBA was injected intraperitoneally daily 30 min before each oral administration of rotenone. Chronic oral administration of rotenone at high doses induced specific nigrostriatal DA neurodegeneration, motor deficits and the up‐regulation of α‐synuclein in the surviving DA neurons. In contrast to the Lewis rat model, cerebral tauopathy was not detected in this mouse model. 4‐PBA inhibited rotenone‐induced neuronal death and decreased the protein level of α‐synuclein. These results suggest that this rotenone mouse model may be useful for understanding the mechanism of DA neurodegeneration in PD, and that 4‐PBA has a neuroprotective effect in the treatment of PD.

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Metadata

Authors
Inden, M., Kitamura, Y., Takeuchi, H., Yanagida, T., Takata, K., Kobayashi, Y., Taniguchi, T., Yoshimoto, K., Kaneko, M., Okuma, Y., Taira, T., Ariga, H., & Shimohama, S.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-02-13
Volume
101
Issue
6
Pages
1491-1504
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2004123088
Cited by
260
References
50
FWCI
6.35
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4‐phenylbutyrate, a chemical chaperone. https://app.cochat.ai/papers/10.1111/j.1471-4159.2006.04440.x
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Inden, M., Kitamura, Y., Takeuchi, H., Yanagida, T., Takata, K., Kobayashi, Y., Taniguchi, T., Yoshimoto, K., Kaneko, M., Okuma, Y., Taira, T., Ariga, H., & Shimohama, S. (2007). Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4‐phenylbutyrate, a chemical chaperone. Journal of Neurochemistry. https://doi.org/10.1111/j.1471-4159.2006.04440.x

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.