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

Mol Neurobiol. 2017 Apr;54(3):2327-2337. doi: 10.1007/s12035-016-9822-5. Epub 2016 Mar 9.


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.

Keywords: 3-Nitropropionic acid; Catecholamines; GABA; Glutamate; Huntington’s disease; L-theanine; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Corpus Striatum / drug effects*
  • Glutamates / pharmacology*
  • Huntington Disease / metabolism
  • Lipid Peroxidation / drug effects*
  • Male
  • Motor Activity / drug effects
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Neuroprotective Agents / pharmacology
  • Nitric Oxide / metabolism*
  • Nitro Compounds / pharmacology*
  • Oxidative Stress / drug effects
  • Propionates / pharmacology*
  • Rats, Wistar
  • Tea*


  • Antioxidants
  • Glutamates
  • Neuroprotective Agents
  • Nitro Compounds
  • Propionates
  • Tea
  • Nitric Oxide
  • theanine
  • 3-nitropropionic acid