The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice

Abstract

Agmatine, a polyamine derived from l-arginine, has been suggested to modulate memory. However, the available evidence regarding the effect of agmatine on the memory of intact animals is contradictory. This study aimed to assess the dose–response effect of subchronic agmatine on passive avoidance memory and anxiety-like parameters of elevated plus maze in adult intact mice. Furthermore, considering the roles of Akt/GSK-3β signaling pathway in memory and Alzheimer’s disease, the hippocampal contents of phosphorylated and total forms of Akt and GSK-3β proteins were determined using the western blot technique. Agmatine was administered intraperitoneally at the doses of 10, 20, 30, 40 and 80 mg/kg/daily to adult male NMRI mice for 10 days after which the behavioral assessments were performed. Upon completion of the passive avoidance test, the hippocampi were removed for western blot analysis to detect the phosphorylated and total levels of Akt and GSK-3β proteins. Results showed the biphasic effect of agmatine on passive avoidance memory; in lower doses (10, 20 and 30 mg/kg), agmatine impaired memory whereas in higher ones (40 and 80 mg/kg) improved it. Though, agmatine in none of the doses affected animals’ anxiety-like parameters in an elevated plus maze. Moreover, the memory-improving doses of agmatine augmented Akt/GSK-3β pathway. This study showed the biphasic effect of agmatine on passive avoidance memory and an augmentation of hippocampal Akt/GSK-3β signaling pathway following the memory-improving doses of this polyamine.

Preventive putative effect of agmatine on cognitive and molecular outcomes in ventral tegmental area of male offspring following physical and psychological prenatal stress

“…Consistent with our results, Ostovan et al. (2022) indicated that high doses of agmatine can improve memory. Therefore, agmatine might provide neuroprotective utility against cognitive impairments induced by PS.…”

“…further showed that agmatine improved memory impairment caused by PS in the male offspring. Consistent with our results,Ostovan et al (2022) indicated that high doses of agmatine can improve memory. Therefore, agmatine might provide neuroprotective utility against cognitive impairments induced by PS.In our study, BDNF level expression was significantly enhanced in the VTA of offspring of mothers exposed to psychological stress when compared to the levels in the control group, and this level wasF I G U R E 5 Assessment of the passive avoidance learning and memory in shuttle box: (a) shock number and (b) step-through latency.…”

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

“…Additionally, NOR is more comparable to the tests used to evaluate human cognition, which increases the ecological validity of this test in comparison to the other animal memory tasks (Lueptow, 2017). Although there are studies indicating that sub-chronic treatment with agmatine (for periods of 10 days or more) has a dose-dependent effect on memory, accordingly a dose of 10 mg/kg was even shown to impair memory (Farokhi et al ., 2022; Os tovan et al ., 2022), i n sho rter periods, the memory-damaging effect of agmatine in doses of 5 and 10 mg has not been observed (Zarifkar et al ., 2010). T heref ore, in general, it seems that agmatine at a dose of 10 mg/kg does not have pro-cognitive effects that can counteract the deleterious effects of Al-NP on memory.…”

“…Moreover, in the streptozotocin-induced memory impairment model, the neuroprotective effect of agmatine was accompanied by an increase in hippocampal GSK-3β phosphorylation (Moosavi et al ., 2014b). In intact animals, sub-chronic administration of agmatine increases hippocampal GSK-3β phosphorylation in addition to its antidepressant and memory-enhancing effects (Freitas et al ., 2014; Ostovan et al ., 2022). Considering the pathological role of GSK-3β in memory disorders, modulation of this kinase by agmatine may play a role in the protective effect of this polyamine against Al-NP.…”