Astrocyte responses to postnatal erythropoietin and nano-erythropoietin treatments in a valproic acid-induced animal model of autism

Abstract

BackgroundDespite ample evidence of the potential protective effects of erythropoietin (EPO) on the developing brain, no study has addressed the effects of postnatal EPO on behaviors and brain tissue of animal models of autism. In the present study, we examined the therapeutic effects of postnatal erythropoietin on stereotypic behaviors and astrocyte responses via glial fibrillary acidic protein (GFAP) and S100 calcium-binding protein B (S100B) immunohistochemistry in a valproic acid (VPA) animal model of autism. Also, we compared the effects of EPO with EPO-loaded solid lipid nanoparticles (NEPO) because the blood-brain barrier has limited permeability to EPO. MethodsPregnant rats received a single dose of VPA (600 mg/kg) at gestational day 12.5. EPO (2000 U/kg) and EPO-loaded solid lipid nanoparticles (NEPO1000 and 2000 U/kg) were injected intraperitoneally from postnatal days 1–5. Repetitive behaviors in male offspring were assessed by a marble burying test. The immune-staining method was performed to evaluate S100B and GFAP-positive cells in the prefrontal cortex and hippocampal CA1 region. ResultsVPA animal models revealed more repetitive behavior and displayed higher astrogliosis in the prefrontal cortex (PFC) and hippocampus (CA1) regions. The repetitive behaviors were ameliorated relatively in VPA groups with NEPO2000 treatment, and astrogliosis was reduced even when VPA rats were treated with a lower dosage of NEPO. ConclusionOur results indicate beneficial effects of postnatal NEPO exposure in the VPA animal model of autism, which proposes it as an early treatment in infants with, or at risk of, autism.