Granulocyte colony-stimulating factor has a sex-dependent positive effect in the maternal immune activation-induced autism model

Abstract

Objective: The medical intervention for autism spectrum disorder (ASD) is restricted to ameliorating comorbid situations. Granulocyte colony-stimulating factor (G-CSF) is a growth factor that enhances the proliferation, differentiation, and survival of hematopoietic progenitor cells. In the present study, we aimed to investigate the effects of G-CSF in a maternal immune activation-induced autism model. Methods: Sixteen female and six male Wistar adult rats were included in the study. After 21 days, 48 littermates (eight male controls, eight female controls, 16 male lipopolysaccharide [LPS]-exposed rats, and 16 female LPS-exposed rats) were divided into groups. Sixteen male LPS-exposed and 16 female LPS-exposed rats were divided into saline and G-CSF treatment groups. Results: In male rats, the LPS-exposed group was found to have significantly higher levels of TNF-alpha, IL-2, and IL-17 than the LPS-exposed G-CSF group. Levels of nerve growth factor, brain PSD-95, and brain GAD67 were higher in the LPS-exposed G-CSF group than in the LPS-exposed group in male rats. In female rats, brain NGF levels were similar between groups. There was no difference between groups in terms of brain GAD 67 levels. Brain PSD-95 levels were higher in the control group than in both the LPS-exposed and LPS-exposed G-CSF groups in female rats. Both neuronal CA1 and neuronal CA2 levels were lower, and the GFAP immunostaining index (CA1) and GFAP immunostaining index (CA3) were higher in the LPS-exposed group than in the LPS-exposed G-CSF group in male rats. However, neuronal count CA1 and neuronal count CA3 values were found to be similar between groups in female rats. Conclusions: The present research is the first to demonstrate the beneficial effects of G-CSF on core symptoms of ASD experimentally depending on male sex. G-CSF can be a good candidate for ameliorating the core symptoms of ASD without serious side effects in males.