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

Autism is a multifactorial neurodevelopment disease and it has not been disclosed asa hypoglutamatergic or hyperglutamathergic disease. Ceftriaxone is an antibiotic that increasesglutamate transporter-1 (GLT-1) expression in the brain in chronic use. In our study we aimed toinvestigate the effects of different doses of ceftriaxone in postnatal period in male mice exposedto valproic acid (VPA) at 12.5th day of pregnancy.

A total of 96 BALB/c male mice were divided into 12 groups (n = 8 animals pergroup). Ceftriaxone (50, 100, 200 mg/kg/d) or saline was given to the male offsprings born frompregnant mice administered VPA and/or saline, between days 47 and 55. Dihydrokainic acid(10 mg/kg), a GLT-1 inhibitor, was administered intraperitoneally to evaluate whether GLT-1mediates the effect of ceftriaxone. Three chamber sociability and social interaction test and therota rod test were performed in all groups on days 54 and 55. GLT-1 levels in the hippocampuswere measured by immunohistochemistry (IHC) and western blotting (WB).

In our study, autism-like behaviors were observed in male offsprings that were exposedto VPA in the intrauterine period. Chronic ceftriaxone administration has no curative effect onbehavioral impairment seen in autism.

Our results show that ceftriaxone did not exert significant therapeutic effect onVPA-induced mouse model of autism.