Neuroprotective Potential of Agmatine in Mitigating Aluminium Chloride-Induced Cognitive Deficits in Rats

Abstract

Introduction: Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by cognitive decline, memory loss, and impaired executive function. AlCl₃ is known to exacerbate oxidative stress and neuroinflammation, contributing to cognitive deficits similar to those observed in AD. Agmatine, a polyamine derived from arginine, has emerged as a potential neuroprotective agent due to its antioxidant, anti-inflammatory, and neuromodulatory properties.

Aim & Objectives: This study aims to evaluate the neuroprotective effects of agmatine against aluminium chloride (AlCl₃)-induced cognitive impairments in male Wistar rats. The objectives include assessing behavioural changes through locomotor activity, the Morris Water Maze, and Object Recognition Task, along with biochemical and neurochemical alterations, focusing on oxidative stress and hippocampal glutamate levels as potential mechanisms underlying cognitive deficits.

Material & Methods: A total of thirty male Wistar rats (n = 6) were split up into five groups. For 21 days, groups II, III, IV, and V were treated with AlCl₃ (100 mg/kg, p.o.) and agmatine at doses of 3 mg/kg (i.p.), 10 mg/kg (i.p.), and 30 mg/kg (i.p.), respectively, while group I (control) was given 0.9% saline. The Morris Water Maze (MWM) and Object Recognition Task (ORT) were used to evaluate cognitive abilities. In brain tissues, biochemical and neurochemical studies were examined.

Result: Prolonged exposure to AlCl₃ raised acetylcholinesterase activity, nitrite, MDA, and decreased GSH levels in the brain, all of which markedly impacted cognitive function. AlCl₃ therapy also resulted in significant decreases in the hippocampal levels of DA, NE, serotonin, GABA, and glutamate.