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L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway

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Abstract

L-theanine is unique amino acid which readily crosses blood brain barrier and possesses neuroprotective potential against neurodegenerative disorders including Huntington disease (HD). HD is characterized by selective loss of GABAergic medium spiny neurons. 3-nitropropionic acid (3-NP) induces a spectrum of HD-like neuropathology in rat striatum and widely used as experimental tool to study HD. Therefore, the present study was intended to investigate the effect of L-theanine against 3-NP-induced striatal toxicity and to explore its possible mechanism. Rats were administered with 3-NP for 21 days. L-theanine was given once a day, 1 h prior to 3-NP treatment for 21 days and L-NAME (10 mg/kg, i.p.), NO inhibitor and L-arginine (50 mg/kg; i.p.), NO precursor were administered 1 h prior to L-theanine treatment. Body weight and behavioral observation were made on weekly basis. On the 22nd day, animals were sacrificed, and the striatum was isolated for biochemical (LPO, GSH, and nitrite), pro-inflammatory cytokines and neurochemical analysis. 3-NP treatment significantly altered body weight, locomotor activity, motor coordination, mitochondrial complex-II activity, oxidative defense, pro-inflammatory mediators, and striatal neurotransmitters level. L-theanine pre-treatment (25 and 50 mg/kg/day, p.o.) significantly prevented these alterations. In addition, concurrent treatment of L-NAME with L-theanine (25 mg/kg/day, p.o.) significantly enhanced protective effect of L-theanine (25 mg/kg/day, p.o.) whereas concurrent treatment of L-arginine with L-theanine (50 mg/kg/day, p.o.) significantly ameliorated the protective effect of L-theanine (50 mg/kg/day, p.o.). The neuroprotective potential of L-theanine involves inhibition of detrimental nitric oxide production and prevention of neurotransmitters alteration in the striatum.

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Abbreviations

3-NP:

3-Nitropropionic acid

5-HIAA:

5-Hydroxy 3-Indole acetic acid

DOPAC:

3,4-dihydroxyphenylacetic acid

HVA:

Homovanillic Acid

HD:

Huntington’s disease

IL:

Inter leukin

MSNs:

Medium spiny neurons

NMDA:

N-methyl d-aspartate

NMDAR:

N-methyl D-aspartate receptor

ROS:

Reactive oxygen species

SDH:

Succinate dehydrogenase

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Acknowledgments

Authors are thankful to the Science and Engineering Board (SERB), Department of Science and Technology, Govt. of India, New Delhi, for providing financial assistance under Fast Track Scheme (DST-SERB-FTYS) to Dr. Puneet Kumar. The Junior Research Fellowship to Mr. Sumit Jamwal is also highly acknowledged.

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Authors and Affiliations

  1. Neuropharmacology Division, Department of Pharmacology, I.S.F College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, 142001, Punjab, India

    Sumit Jamwal & Puneet Kumar

  2. Research Scholar, I. K Gujral Punjab Technical University, Jalandhar, India

    Sumit Jamwal

Authors
  1. Sumit Jamwal
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  2. Puneet Kumar
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Correspondence to Puneet Kumar.

Ethics declarations

The experimental protocol was reviewed and approved by the Institutional Animal Ethics Committee (ISFCP/IAEC/M5/2012/P39), and experiments were conducted in compliance with the guidelines of the Indian National Science Academy (INSA) for the use and care of experimental animals.

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The authors declare that they have no conflict of interests.

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Jamwal, S., Kumar, P. L-theanine, a Component of Green Tea Prevents 3-Nitropropionic Acid (3-NP)-Induced Striatal Toxicity by Modulating Nitric Oxide Pathway. Mol Neurobiol 54, 2327–2337 (2017). https://doi.org/10.1007/s12035-016-9822-5

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