L-THEANINE SPARES STRIATAL NEURONS FROM 3-NP–INDUCED STRIATAL NEUROTOXICITY: ROLE OF NITRIC OXIDE PATHWAY

Abstract

L-theanine is unique amino acid which readily crosses blood brain barrier and posses neuroprotective potential against neurodegenerative disorders including Huntington Disease (HD). HD is characterized by selective loss of GABAergic medium spiny neurons. Therefore, the present study was intended to investigate the effect of L-theanine against 3-NP induced striatal toxicity. Rats were administered with 3-NP for 21 days. L-theanine was given once a day, 1 hour prior to 3-NP treatment for 21 days and L-NAME (NOS inhibitor) and L-arginine (NOS activator) were administered 1 hour prior to L-theanine treatment. Body weight, behavioral parameters (locomotor activity, grip strength, narrow beam walk) observation was done on 1st, 7th, 14th, and 21st day after 3-NP treatment. On 22nd day, animals were sacrificed and rat striatum was isolated for biochemical (mitochondrial complex- II, LPO, GSH and nitrite), pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and neurochemical analysis (GABA, Glutamate, DA, NE, 5-HT, DOPAC, HVA, 5-HIAA and Adenosine). 3-NP treatment significantly altered body weight, locomotor activity, motor coordination, mitochondrial complex-II activity, oxidative defence, pro-inflammatory mediators (TNF-α, IL-6 and IL-1β), and striatal neurotransmitters level i.e. GABA, glutamate, catecholamines, adenosine, inosine and hypoxanthine whereas L-theanine treatment (25 & 50 mg/kg/day, p.o.) significantly prevented these alterations. 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 decreased 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 striatum.