Objective: To evaluate the neuroprotective efficacy of L-theanine, an unique amino acid with neuroprotective properties, for its beneficial potential if any, in quinolinic acid induced Huntington’s like symptoms in rats.

Background: Huntington Disease is hyperkinetic movement disorder characterized by selective and immense degradation of GABAergic medium spiny neurons in striatum. Quinolinic acid induced neurotoxicity involves a cascade of events such as excitotoxicity, ATP depletion, oxidative stress, neuroinflammation as well as selective GABAergic neuronal loss. L-theanine has been reported to provide neuroprotection in animals model of cerebral ischemia and Alzheimer’s disease.

Methods: Rats were administered with QA (200 nmol/2µl saline) bilaterally on 0 day. L-theanine was given once a day at dose of 25 & 50 mg/kg orally for 21 days and L-NAME (NOS inhibitor) and L-arginine (NOS activator) were administered 1 hour prior to L-theanine treatment. Behavioral parameters (body weight, locomotor activity, grip strength, narrow beam walk) observations were done on 1st, 7th, 14th, 21st day after QA treatment. On 21st day, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH, Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, dopamine, serotonin, DOPAC, HVA and 5-HIAA).

Results: Quinolinic acid treatment significantly altered body weight, locomotor activity, motor coordination, oxidative defence (increased LPO, Nitrite and decreased GSH), pro-inflammatory levels (TNF-α, IL-6 and IL-1β), GABA, glutamate, catecholamines level (dopamine, serotonin and their metabolites). 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.).

Conclusions: The neuroprotective potential of L-theanine involves inhibition of detrimental nitric oxide production, anti-oxidant property and prevention of neurotransmitters alteration in striatum.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-potential-of-l-theanine-against-excitotoxic-neuronal-death-induced-by-quinolinic-acid-possible-neurotransmitters-and-nitric-oxide-modulation-mechanism/