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Neuroprotective Effects of (-)-Epigallocatechin-3-gallate in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

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Abstract

The purpose of this study is to evaluate neuroprotective effects of (-)-Epigallocatechin-3-gallate (EGCG) in a transgenic mouse model of Amyotrophic lateral sclerosis (ALS). SOD1-G93A transgenic mice and wild-type mice were randomly divided into EGCG-treated groups (10 mg/kg, p.o) and vehicle-treated control groups. Rotarod measurement was performed to assess the motor function of mice starting at the age of 70 days. Nissl staining to examine the number of motor neurons and CD11b immunohistochemical staining to evaluate activation of microglia in the lumbar spinal cords were conducted at the age of 120 days. In addition, for further observation of regulation of cell signaling pathways by EGCG, we used immunohistochemical analysis for nuclear factor kappa B (NF-κB) and cleaved caspase-3 as well as western blot analysis to determine the expression of nitric oxide synthase (iNOS) and NF-κB in the spinal cord. This study demonstrated that oral administration of EGCG beginning from a pre-symptomatic stage significantly delayed the onset of disease, and extended life span. Furthermore, EGCG-treated transgenic mice showed increased number of motor neurons, diminished microglial activation, reduced immunohistochemical reaction of NF-κB and cleaved caspase-3 as well as reduced protein level of iNOS and NF-κB in the spinal cords. In conclusion, this study provides further evidences that EGCG has multifunctional therapeutic effects in the mouse model of ALS.

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Acknowledgments

This work was supported by National Science Foundation of China (No. 30370491), a research grant (E03003) from High Education Commission of Shanghai Municipality and Research Fund (03DZ14021) from Science and Technology Commission of Shanghai Municipality.

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Authors and Affiliations

  1. Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China

    Zhihao Xu, Xuping Li, Guangrui Luo, Liang Li & Weidong Le

  2. Institute of Neurology, Ruijin Hospital, Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China

    Sheng Chen & Weidong Le

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  1. Zhihao Xu
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  2. Sheng Chen
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  3. Xuping Li
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  4. Guangrui Luo
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  5. Liang Li
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Correspondence to Weidong Le.

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Xu, Z., Chen, S., Li, X. et al. Neuroprotective Effects of (-)-Epigallocatechin-3-gallate in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis. Neurochem Res 31, 1263–1269 (2006). https://doi.org/10.1007/s11064-006-9166-z

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  • DOI: https://doi.org/10.1007/s11064-006-9166-z

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