The effects of postnatal erythropoietin and nano-erythropoietin on behavioral alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat model of autism.

Researchers tested a medication called nano-erythropoietin in young rats that had been exposed to a chemical that causes autism-like behaviors. The treatment improved the rats' behaviors and protected brain cells. It also helped fix problems with a brain protein that controls how nerve cells communicate. This early research suggests this type of treatment might help with autism, but much more research is needed before it could be considered for humans.

This preclinical study investigated the effects of erythropoietin (EPO) and nano-erythropoietin (NEPO) on autism-like behaviors in a rat model using valproic acid (VPA) exposure. Male rat offspring received postnatal EPO or NEPO treatment (days 1-5) after prenatal VPA exposure. High-dose NEPO improved autism-associated behaviors and showed neuroprotective effects in the hippocampus. The treatment reversed abnormal expression of K-Cl co-transporter 2 (KCC2), a protein involved in GABA neurotransmitter function and excitatory/inhibitory balance in the brain.

The findings support the excitatory/inhibitory imbalance theory of autism and suggest KCC2-targeted interventions may represent a novel early treatment approach.

This preclinical research identifies nano-erythropoietin as a potential early intervention target through KCC2 modulation. However, extensive research including safety studies, dose optimization, and human trials would be required before clinical application. The KCC2 pathway may represent a novel therapeutic approach for addressing excitatory/inhibitory imbalance in autism.

Animal model study with unclear sample size. VPA-induced autism model may not fully represent human autism complexity. No comparison to standard treatments or long-term outcomes reported. Requires extensive safety and efficacy testing before human application.

In this study, based on the excitatory/inhibitory imbalance theory of autism, the time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in adjustment GABA switch, and brain permeability to erythropoietin (EPO), the effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in the valproic acid (VPA) rat model of autism. The VPA was administered for animal modeling of autism at gestational day (GD) 12.5 (600 mg/kg). Male offsprings were injected with EPO and NEPO in a clinically proper postnatal dosing regimen on postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of the first month. Then animals were sacrificed, and neuron morphology and KCC2 expression were examined by Nissl staining and Western blot.

According to our findings, high-dose NEPO improved autism-associated phenotypes. Neuroprotective effects of EPO and NEPO have been shown in the hippocampus. Postnatal NEPO treatment reversed KCC2 expression abnormalities induced by prenatal VPA. Our results might support the role of KCC2 in ASD and the excitatory/inhibitory imbalance hypothesis.

We suggested Nano- erythropoietin and other KCC2 interventions as a new approach to the early treatment and prevention of autism.