Effect of AILE on Working and Reference Memory of Ketamine Induced Memory Impaired Male Wistar Rats in Radial Arm Maze (RAM)
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Abstract
Background: Memory impairment involves a decline in memory, cognition, behavior and daily functioning. Conventional treatments often fall short due to the complex mechanisms underlying memory loss, diminishing effectiveness over time and having significant side effects. In this context, medicinal herbs have gained attention for their broad therapeutic benefits and lower risk of adverse effects. Among them, Azadirachta indica leaf extract (AILE) is notable for its diverse biological properties, making it a promising candidate for addressing cognitive decline. Objective: The study aimed to evaluate the effects of AILE on spatial working and reference memory in male Wistar rats with ketamine-induced memory impairment. Ketamine, a known NMDA receptor antagonist, was used to induce cognitive deficits, which were assessed using the Radial Arm Maze (RAM). Methods: This experimental study was conducted in the Department of Physiology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, using 30 male Wistar rats (200±50 g body weight) sourced from the university's central animal house. The rats were divided into three groups: Group 1 (G1) normal memory, Group 2 (G2) memory impaired, Group 3 (G3) experimental, respectively. Ethical approval for this research was obtained from the Institutional Review Board (IRB) of BSMMU. Data were analyzed using ANOVA, Bonferroni post hoc tests, and Student's paired t-test with significance set at p≤0.05. Results: In the RAM test, ketamine-treated rats exhibited a significant increase in both working memory errors and reference memory errors (p≤0.001), indicating substantial memory impairment. However, rats treated with AILE showed a significant reduction in both working memory errors and reference memory errors (p≤0.001) compared to the ketamine-only group. These results suggest that AILE effectively mitigates ketamine-induced cognitive deficits, improving both working and reference memory performance in the RAM. Conclusion: AILE demonstrated significant neuroprotective effects against ketamine-induced memory impairment, likely through modulation of NMDA receptor function, reduction of oxidative stress, and inhibition of apoptotic pathways. These findings suggest AILE's potential as a therapeutic agent for cognitive deficits involving NMDA receptor dysfunction.
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