The effects of aminoguanidine on hippocampal cytokines, amyloid beta, brain-derived neurotrophic factor, memory and oxidative stress status in chronically lipopolysaccharide-treated rats

Abstract

Introduction: In the present study, the effects of aminoguanidine (AMG) on hippocampal cytokines, amyloid beta (Aβ), brain-derived neurotrophic factor, oxidative stress status and memory in chronically lipopolysaccharide (LPS) treated rats were investigated.

Methods: The rats were divided into five groups and were treated: (1) Control (Saline), (2) LPS (1 mg/kg), (3-5) LPS- AMG50, LPS-AMG100, and LPS-AMG150 (AMG 50, 100 and 150 mg/kg 30 min before LPS injection). The treatment started five weeks prior to the behavioral experiments and continued during the behavioral tests (LPS injection two hours before each behavioral evaluation). Finally, the tissue was removed for biochemical measurements.

Results: The escape latency in Morris water maze test and the latency to enter the dark compartment in passive avoidance test in LPS group were significantly greater than the control group (P < 0.001), while, in LPS-AMG 100 and LPS-AMG150 groups they were less than LPS group (P < 0.001). Malondialdehyde (MDA), NO metabolites of hippocampal and cortical tissues and interleukin-6 (IL-6), Aβ and tumor necrosis factor-α (TNFα) concentration in the hippocampus of LPS group were higher than control group (P < 0.001-P < 0.05). However, in LPS-AMG 100 and LPS-AMG150 group they were lower than LPS group (P < 0.001-P < 0.05). The thiol content and the activities of catalase (CAT) and superoxide dismutase (SOD) in both cortical and hippocampal tissues of LPS group were reduced compared to the control group (P < 0.001-P < 0.05). These factors enhanced in LPS-AMG 100 and LPS-AMG150 groups compared to LPS (P < 0.001-P < 0.05). The hippocampal content of brain-derived neurotrophic factor (BDNF) in LPS group was significantly lower compared to the control group (P < 0.001). All treated groups had higher BDNF content in comparison to LPS group (P < 0.01-P < 0.001).

Conclusion: The findings indicated that the protective effects of AMG against LPS-induced memory were accompanied by decreasing of inflammatory cytokines, Aβ, oxidative stress and increasing of anti-inflammatory mediators and BDNF.

Keywords: Aminoguanidine; Amyloid beta; Brain-derived neurotrophic factor; Cytokines; Learning; Lipopolysaccharide; Memory.