Curcumin ameliorates aluminum oxide nanoparticle-induced memory deficit by regulating the hippocampal p38 signaling pathway in mice.

Abstract

Objectives: Exposure to aluminum (Al) has been shown to be strongly associated with the pathogenesis of Alzheimer's disease (AD). Recent evidence indicates that the toxicity of Al nanoparticle (Al-NP) is far greater than Al itself due to its particle size. Epidemiological studies suggest that curcumin lower the prevalence of AD. MAPKs (ERK, p38 and JNK) were suggested to be involved in AD pathology and memory impairment. The present study aimed to evaluate if curcumin has the ability to protect against behavioral deficits induced by subcutaneously administered Al-NP in mice. Furthermore, the levels of phosphorylated and total hippocampal MAPKs were assessed using western blottechnique.

Methods: Al-NP (10 mg/kg/s.c.) was administered to adult male NMRI mice for 10 days with or without curcumin in doses of 2.5 or 25 mg/kg/oral gavage). Memory was assessed using passive avoidance apparatus and anxiety-like behavior was evaluated using elevated plus maze. Following the behavioral tasks, western blot analysis was performed on the hippocampal tissues to detect the levels of phosphorylated and total MAPKs.

Results: The results revealed that Al-NP deteriorated memory with no significant effect on anxiety-like behaviors. Additionally, it activated hippocampal p38 signaling pathway with no effect on ERK and JNK. Curcumin treatment at the dose of 25 mg/kg restored memory and p38 activation.

Discussion: This study suggests that subcutaneous Al-NP administration impairs memory and hippocampal p38 signaling with no effect on ERK and JNK. Co-administration of curcumin restored Al-NP induced memory impairment and hippocampal p38 phosphorylation.