Abstract
Purpose: Autism is a multifactorial neurodevelopment disease and it has not been disclosed as a hypoglutamatergic or hyperglutamathergic disease. Ceftriaxone is an antibiotic that increases glutamate transporter-1 (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. 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/d) 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 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 (IHC) and western blotting (WB). Results: In our study, autism-like behaviors were observed in male offsprings 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 VPA-induced mouse model of autism.
Highlights
Autism spectrum disorder (ASD) is a common and serious neurodevelopmental disorder characterized by two main symptoms; lack of social communication skills and repetitive behavior
Our results show that ceftriaxone did not exert significant therapeutic effect on valproic acid-induced mouse model of autism
Based on this information we aimed to investigate the effect of ceftriaxone in male offspring exposed to valproic acid (VPA) in the embryonic period and determine whether ceftriaxone-induced increase in GLT-1 levels in the brain has any u effect on behavioral impairment in ASD
Summary
Autism spectrum disorder (ASD) is a common and serious neurodevelopmental disorder characterized by two main symptoms; lack of social communication skills and repetitive behavior. Offsprings whose mothers received a single dose of 600 mg/kg VPA injection at day 12.5 of gestation are considered to be autistic and used in experimental studies.[6] It is not known exactly how VPA causes autistic behaviors. Determination of folic acid metabolism, inhibition of histone deacetylation and increased oxidative stress may play roles in this process.[6,7,8] t The pathophysiology of autism is unclear and unbalance of GABA and glutamate ratios may cause ASD.[9] In autistic patients, it has been shown that plasma GABA levels are higher and glutamate/GABA ratio is lower.[10] ip there are studies reporting the contrary.[11] Glutamate is the most important excitatory neurotransmitter in the brain, and glutamate transporters regulate extracellular glutamate homeostasis. In addition we showed that chronic ceftriaxone injection increased GLT-1 expression in s hippocampus in mice[15]
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