Administration of agmatine prior to physical or psychological stress in pregnant mice ameliorates behavioural and cognitive deficits in female offspring

Abstract

Physical or psychological stress experienced by a mother during gestation is often associated with serious behavioural and cognitive deficits in newborns. Investigations of protective agents, which could prevent the adverse outcomes of prenatal stress (PS), are warranted. Agmatine is a neurotransmitter putatively involved in the physiological response to stress, and exogenous administration of agmatine has been shown to produce a variety of neuroprotective effects. In this study, we aimed to assess whether prenatal agmatine exposure could ameliorate behavioural and cognitive deficits in female offspring born to prenatally stressed mice. Pregnant Swiss Webster (SW) mice were exposed to physical or psychological stress from the 11th to 17th days of gestation. Agmatine (37.5 mg/kg, i.p.) was administrated 30 min before the induction of stress for seven consecutive days. The pups were assessed using a variety of behavioural tests and molecular assays on postnatal days 40 to 47. Agmatine attenuated impairments in locomotor activity, anxiety‐like behaviour, and drug‐seeking behaviour associated with both physical and psychological PS. Furthermore, agmatine reduced PS‐induced impairments in passive avoidance memory and learning. Neither PS nor agmatine treatment affected the mRNA expression level of hippocampal brain‐derived neurotrophic factor (BDNF) or tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). Taken together, our findings highlight the protective effects of prenatally administered agmatine on PS‐mediated behavioural and cognitive deficits of the offspring. Future studies are needed to elucidate the underlying mechanisms, which could allow for more targeted prenatal treatments.

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

“…Considering that several previous studies have indicated that PS might differentially affect each sex (Gué et al., 2004; GhotbiRavandi et al., 2021), the sex‐dependent effects of PS must be taken into account. The findings of our present study are comparable to our recent findings in female offspring (Hassanshahi et al., 2023). Similar to what we observed in the male offspring, PS resulted in impaired locomotor activity, increased anxiety‐like behavior, heightened drug‐seeking behavior, and impaired passive avoidance memory in the female offspring, which were prevented with the administration of agmatine during the pregnancy (Hassanshahi et al., 2023).…”

“…The findings of our present study are comparable to our recent findings in female offspring (Hassanshahi et al., 2023). Similar to what we observed in the male offspring, PS resulted in impaired locomotor activity, increased anxiety‐like behavior, heightened drug‐seeking behavior, and impaired passive avoidance memory in the female offspring, which were prevented with the administration of agmatine during the pregnancy (Hassanshahi et al., 2023). Moreover, our findings indicate that PS had no detrimental effects on hippocampal BDNF both in male and female offsprings.…”

The prenatal use of agmatine prevents social behavior deficits in VPA‐exposed mice by activating the ERK/CREB/BDNF signaling pathway

“…Previous studies have indicated that postnatal administration of AGM to pups in the VPA animal model can alleviate ASD‐like symptoms (Kim et al, 2017). Furthermore, scholars have investigated the prenatal application of AGM, revealing that administering AGM to pregnant mice during simulated prenatal stress improves the behavior and cognitive deficits in female offspring (Hassanshahi et al, 2023). However, there is currently no report on the prenatal administration of AGM in the VPA animal model of ASD.…”