N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum-induced spatial memory deficit in rats

Fernandes, Joylee and Mudgal, Jayesh and Rao, Mallikarjuna C and Arora, Devinder and Mallik, Sanchari Basu and Pai, KSR and Nampoothiri, Madhavan (2018) N-acetyl-L-tryptophan, a substance-P receptor antagonist attenuates aluminum-induced spatial memory deficit in rats. Toxicology Mechanisms and Methods, 28 (5). pp. 328-334.

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Abstract

Neuroinflammation plays an important role in the pathophysiology of Alzheimer’s disease. Neurokinin substance P is a key mediator which modulates neuroinflammation through neurokinin receptor. Involvement of substance P in Alzheimer’s disease is still plausible and various controversies exist in this hypothesis. Preventing the deleterious effects of substance P using N-acetyl-L-tryptophan, a substance P antagonist could be a promising therapeutic strategy. This study was aimed to evaluate the effect of N-acetyl-L-tryptophan on aluminum induced spatial memory alterations in rats. Memory impairment was induced using aluminum chloride (AlCl3) at a dose of 10mg/kg for 42 d. After induction of dementia, rats were exposed to 30 and 50mg/kg of N-acetyl-L-tryptophan for 28 d. Spatial memory alterations were measured using Morris water maze. Acetylcholinesterase activity and antioxidant enzyme glutathione level were assessed in hippocampus, frontal cortex and striatum. The higher dose of N-acetyl-L-tryptophan (50 mg/kg) significantly improved the aluminum induced memory alterations. N-acetyl-L-tryptophan exposure resulted in significant increase in acetylcholinesterase activity and glutathione level in hippocampus. The neuroprotective effect of N-acetyl-L-tryptophan could be due to its ability to block substance P mediated neuroinflammation, reduction in oxidative stress and anti-apoptotic properties. To conclude, N-acetyl-L-tryptophan may be considered as a novel neuroprotective therapy in Alzheimer’s disease.

Item Type: Article
Uncontrolled Keywords: N-acetyl-L-tryptophan; aluminum; dementia; oxidative stress.
Subjects: Pharmacy > MCOPS Manipal > Pharmacology
Depositing User: KMC Library
Date Deposited: 17 May 2018 09:26
Last Modified: 17 May 2018 09:26
URI: http://eprints.manipal.edu/id/eprint/150971

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