The Effect of Ceftriaxone in Valproic Acid-Induced Mouse Model of Autism

Abstract

Purpose: Autism is a multifactorial neurodevelopment disease and it has not been disclosed as a hypoglutamatergic or hyerglutamathergic disease. Ceftriaxone is an antibiotic that increases GLT-1 expression in the brain in chronic use. In our study we aimed to investigate the effects of different doses of ceftriaxone in postnatal period in male mice exposed to valproic acid (VPA) at 12.5th day of pregnancy. Material and Methods: A total of 96 Balb/c male mice were divided into 12 groups (n=8 animals per group). Ceftriaxone (50, 100, 200 mg/kg/day) or saline was given to the male offsprings born from pregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid (10 mg/kg), a glutamate transporter-1 (GLT-1) inhibitor, was administered intraperitoneally to evaluate whether GLT-1 mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and the rota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampus were measured by immunohistochemistry and western blotting. Results: In our study, autism-like behaviors were observed in male offspings that were exposed to VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect on behavioral impairment seen in autism. Conclusion: Our results show that ceftriaxone did not exert significant therapeutic effect on valproic acid-induced mouse model of autism.