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

Abstract Background According to reports, prenatal exposure to valproic acid can induce autism spectrum disorder (ASD)‐like symptoms in both humans and rodents. However, the exact cause and therapeutic method of ASD is not fully understood. Agmatine (AGM) is known for its neuroprotective effects, and this study aims to explore whether giving agmatine hydrochloride before birth can prevent autism‐like behaviors in mouse offspring exposed prenatally to valproic acid. Methods In this study, we investigated the effects of AGM prenatally on valproate (VPA)‐exposed mice. We established a mouse model of ASD by prenatally administering VPA. From birth to weaning, we evaluated mouse behavior using the marble burying test, open‐field test, and three‐chamber social interaction test on male offspring. Results The results showed prenatal use of AGM relieved anxiety and hyperactivity behaviors as well as ameliorated sociability of VPA‐exposed mice in the marble burying test, open‐field test, and three‐chamber social interaction test, and this protective effect might be attributed to the activation of the ERK/CREB/BDNF signaling pathway. Conclusion Therefore, AGM can effectively reduce the likelihood of offspring developing autism to a certain extent when exposed to VPA during pregnancy, serving as a potential therapeutic drug.