Agmatine prevents the memory impairment and the dysfunction of hippocampal GSK‐3β and ERK signaling induced by Aluminum nanoparticle in mice

Abstract Background The growing usage of Aluminum nanoparticles (Al‐NP) and its exposure may influence body function. Considering the proposed relationship between Al and the pathogenesis of Alzheimer’s disease (AD) and the concern about the effect of this nanoparticle on brain health and cognitive function, the use of neuroprotective agents might be helpful. According to the reported neuroprotective effects of agmatine, in the present study the possible protective effect of agmatine was assessed in mice model of Al‐NP induced memory impairment. was investigated in the present study. In addition, due to the roles of hippocampal Glycogen synthase kinase 3 beta (GSK‐3β) and ERK signaling in memory and its disorders, these pathways were also investigated. Method Al‐NP (10 mg/kg/p.o.) with/without agmatine (5 or 10 mg/kg/i.p.) was administered to adult male NMRI mice for 5 days. Novel object recognition (NOR) test session was used to assess cognitive function. Following the behavioral assessments, the hippocampi were used to determine the phosphorylated and total levels of GSK‐3β and ERK as well as GAPDH using western blot analysis. Result The results showed that Al‐NP impaired NOR memory in mice while agmatine 10 mg/kg prevented the memory deficit induced by Al‐NP. Furthermore, Al‐NP activated GSK‐3β as well as ERK signals within the hippocampus while agmatine prevented the effects of Al‐NP on GSK‐3β and ERK signals within the hippocampus. Conclusion Besides supporting the neuroprotective effects of agmatine, these findings suggest the possibility of the connection of hippocampal GSK‐3β and ERK signaling in the neuroprotective effect of this polyamine against Al‐NP.