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Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models

  • Authors:
    • Jing Zhang
    • Bohao Sun
    • Jifeng Yang
    • Zhuo Chen
    • Zhengzheng Li
    • Nan Zhang
    • Hongzhi Li
    • Luxi Shen

  • View Affiliations

  • Published online on: January 17, 2022     https://doi.org/10.3892/mmr.2022.12607
  • Article Number: 91

  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Animal models for Parkinson's disease (PD) are very useful in understanding the pathogenesis of PD and screening for new therapeutic approaches. The present study compared two commonly used neurotoxin‑induced mouse models of chronic PD to guide model selection, explore the pathogenesis and mechanisms underlying PD and develop effective treatments. The chronic PD mouse models were established via treatment with rotenone or 1‑methyl‑4‑phenyl‑1,2,3,6-tetrahydropyridine (MPTP) for 6 weeks. The effects of rotenone and MPTP in the mice were compared by assessing neurobehavior, neuropathology and mitochondrial function through the use of the pole, rotarod and open field tests, immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), ionized calcium‑binding adapter molecule 1 (Iba‑1), neuronal nuclear antigen (NeuN) and (p)S129 α‑synuclein, immunofluorescence for GFAP, Iba‑1 and NeuN, western blotting for TH, oxygen consumption, complex I enzyme activity. The locomotor activity, motor coordination and exploratory behavior in both rotenone and MPTP groups were significantly lower compared with the control group. However, behavioral tests were no significant differences between the two groups. In the MPTP group, the loss of dopaminergic (DA) neurons in the substantia nigra (SN) pars compacta, the reduction of the tyrosine hydroxylase content in the SN and striatum and the astrocyte proliferation and microglial activation in the SN were more significant compared with the rotenone group. Notably, mitochondrial‑dependent oxygen consumption and complex I enzyme activity in the SN were significantly reduced in the rotenone group compared with the MPTP group. In addition, Lewy bodies were present only in SN neurons in the rotenone group. Although no significant differences in neurobehavior were observed between the two mouse models, the MPTP model reproduced the pathological features of PD more precisely in terms of the loss of DA neurons, decreased dopamine levels and neuroinflammation in the SN. On the other hand, the rotenone model was more suitable for studying the role of mitochondrial dysfunction (deficient complex I activity) and Lewy body formation in the SN, which is a characteristic pathological feature of PD. The results indicated that MPTP and rotenone PD models have advantages and disadvantages, therefore one or both should be selected based on the purpose of the study.
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March-2022
Volume 25 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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  • CiteScore: 7.6
  • CiteScore Rank: Q1: #82/347 Biochemistry, Genetics and Molecular Biology
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Spandidos Publications style
Zhang J, Sun B, Yang J, Chen Z, Li Z, Zhang N, Li H and Shen L: Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models. Mol Med Rep 25: 91, 2022.
APA
Zhang, J., Sun, B., Yang, J., Chen, Z., Li, Z., Zhang, N. ... Shen, L. (2022). Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models. Molecular Medicine Reports, 25, 91. https://doi.org/10.3892/mmr.2022.12607
MLA
Zhang, J., Sun, B., Yang, J., Chen, Z., Li, Z., Zhang, N., Li, H., Shen, L."Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models". Molecular Medicine Reports 25.3 (2022): 91.
Chicago
Zhang, J., Sun, B., Yang, J., Chen, Z., Li, Z., Zhang, N., Li, H., Shen, L."Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models". Molecular Medicine Reports 25, no. 3 (2022): 91. https://doi.org/10.3892/mmr.2022.12607