The Impact of Sitagliptin on Sodium Valproate-Induced Autism in a Mouse Model

Abstract

Background:Autism spectrum disorder (ASD), a neurodevelopmental disease, is described by problems with social interaction and communication that arise at an early age. The only approved drugs for the treatment of ASD are risperidone and aripiprazole. Objectives:The aim of the article is to explore the potential therapeutic effects of sitagliptin on the induced offspring model of autism. Also, to evaluate the effect of sitagliptin on interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Materials and Methods:We induced the disorder in mice by injecting pregnant mice with sodium valproate (600 mg/kg). Prenatal sodium valproate–exposed mice were split into four different groups, with two experimental groups taking sitagliptin (10 mg/kg and 15 mg/kg) and risperidone (1 mg/kg), and a control group receiving normal saline. Behavioral tests, including social interaction assessments were divided into three phases: habituation, familiarization, and testing, and lasted for 15 min, were conducted on postnatal day 65; also, anti-inflammatory marker assessments like TNF-α and IL-6 were conducted on postnatal day 66. Results:The study found that sitagliptin significantly improved behavioral disorders (social communication) and reduced neuro-inflammation in the brain. Sitagliptin therapy forcefully enhanced the cognitive function of ASD mice by regulating neurogenesis that could be connected with the powerful antioxidant and anti-inflammatory actions that sitagliptin possesses. Conclusion:Sitagliptin showed potent anxiolytic and anti-inflammatory properties that improved behavioral activities in the mice. These findings suggest that sitagliptin could be promising a potential treatment option for individuals with ASD.

Keywords

• autism
• risperidone
• sitagliptin
• sodium valproate