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L-Theanine Ameliorated Rotenone-Induced Parkinsonism-like Symptoms in Rats

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Abstract

Rotenone (RO)-induced neurotoxicity exhibits pathophysiological features similar to those reported in patients with Parkinson’s disease (PD), such as nitrosative and oxidative stress, mitochondrial dysfunction, and neural cytoarchitecture alterations in the substantia nigra pars compacta (SNpc)/striatum (ST), which has been used for decades as an animal model of PD in humans. L-Theanine (LT), a major amino acid component of green tea, exhibits potent antioxidant and anti-inflammatory activities and protects against various neural injuries. We investigated the potential therapeutic effects of LT on RO-induced behavioral and neurochemical dysfunction in rats and the neuroprotective mechanisms underlying these effects. Unilateral stereotaxic intranigral infusion of RO into the SNpc to induce PD-like manifestations induced significant behavioral impairment as evaluated using an open field test, rotarod test, grip strength measurement, and beam-crossing task in rats. LT treatment (300 mg/kg i.p., 21 days) ameliorated most RO-induced behavioral impairments. In addition, LT treatment reduced nitric oxide level and lipid peroxidation production, increased mitochondrial function and integrity, as well as the activities of mitochondrial complexes I, II, IV, and V, and reduced the levels of neuroinflammatory and apoptotic markers in the SNpc and ameliorated the levels of catecholamines, GABA and glutamate in the ST induced by RO. These results demonstrate the possible therapeutic effects of LT against RO-induced behavioral impairments, including antioxidative effects, prevention of mitochondrial dysfunction, prevention of neurochemical deficiency, anti-neuroinflammatory effects, and anti-apoptotic effects. This is the first report on the neuroprotective effect of LT against RO-induced behavioral impairments, and the above evidence provides a potential clinically relevant role for LT in the management of human PD.

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The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the Mackay Memorial Hospital (MMH-107–89) and Shin Kong Wu Ho-Su Memorial Hospital (2018SKHADR022).

Author information

Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, Taitung Br. of Mackay Memorial Hospital, Taitung, 95054, Taiwan, Republic of China

    Cheng-Neng Chen

  2. Department of Medicine, Mackay Medical College, New Taipei City, 252, Taiwan, Republic of China

    Cheng-Neng Chen

  3. Department of Anesthesia, En Chu Kon Hospital, Sanshia District , New Taipei City, 23702, Taiwan, Republic of China

    Mao-Hsien Wang

  4. Department of Psychiatry, Yuan-Shan Br. of Taipei Veteran General Hospital, Yilan County, 26604, Taiwan, Republic of China

    Hung-Sheng Soung

  5. Department of Biomedical Engineering, National Defense Medical Center, Taipei, 11490, Taiwan, Republic of China

    Hung-Sheng Soung

  6. Department of Neurosurgery, Taipei Medical University Hospital, Taipei Medical University, Taipei, 110, Taiwan, Republic of China

    Shu-Mei Chen

  7. Department of Surgery, School of Medicine, Taipei Medical University, Taipei, 110, Taiwan, Republic of China

    Shu-Mei Chen

  8. China Medical University Hospital, No. 2, Yu-Der Rd, Taichung City, 404332, Taiwan, Republic of China

    Chih-Hsiang Fang

  9. Trauma and Emergency Center, North Dist, China Medical University Hospital, No.2, Xueshi Rd, Taichung City, 404018, Taiwan, Republic of China

    Chih-Hsiang Fang

  10. Institute of Biomedical Engineering, National Taiwan University, Taipei, 10051, Taiwan, Republic of China

    Yi-Wen Lin

  11. Department of Anesthesiology, Su Memorial Hospital, Shin Kong Wu Ho, Taipei, 11101, Taiwan, Republic of China

    Hsiang-Chien Tseng

  12. School of Medicine, Fu Jen Catholic University, New Taipei City, 24205, Taiwan, Republic of China

    Hsiang-Chien Tseng

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  1. Cheng-Neng Chen
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  2. Mao-Hsien Wang
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  4. Shu-Mei Chen
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  7. Hsiang-Chien Tseng
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Contributions

CNC collected the data, executed the majority of the experiments, and drafted the manuscript. MHW, HSS, SMC, CHF, and YWL contributed to the active discussion of experimental design and performing of the animal study. HCT supervised the study, assisted with study conceptualization, and made a substantial contribution to the revision of the manuscript. All authors have read and approved the final submitted manuscript.

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All animal procedures and experiments were performed following a protocol approved by the National Taiwan University College of Medicine and Public Health Institutional Animal Care and Use Committee (IACUC no. 20180026).

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The authors declare no competing interests.

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Chen, CN., Wang, MH., Soung, HS. et al. L-Theanine Ameliorated Rotenone-Induced Parkinsonism-like Symptoms in Rats. Neurotox Res 40, 241–258 (2022). https://doi.org/10.1007/s12640-021-00451-w

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  • DOI: https://doi.org/10.1007/s12640-021-00451-w

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