粒细胞集落刺激因子在母体免疫激活诱导的自闭症模型中具有性别依赖性的积极作用。

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

机构信息

Department of Pediatrics, Istanbul Medeniyet University, İstanbul, Turkey.

Department of Psychiatry, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey.

出版信息

Int J Dev Neurosci. 2022 Dec;82(8):716-726. doi: 10.1002/jdn.10221. Epub 2022 Aug 12.

DOI:10.1002/jdn.10221

PMID:35904498

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-α, 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.

摘要

目的

自闭症谱系障碍（ASD）的医学干预仅限于改善共病情况。粒细胞集落刺激因子（G-CSF）是一种生长因子，可增强造血祖细胞的增殖、分化和存活。本研究旨在探讨 G-CSF 在母体免疫激活诱导的自闭症模型中的作用。

方法

纳入 16 只雌性和 6 只雄性 Wistar 成年大鼠进行研究。21 天后，48 只幼鼠（8 只雄性对照、8 只雌性对照、16 只脂多糖 [LPS]-暴露雄性大鼠和 16 只 LPS 暴露雌性大鼠）被分为不同组。16 只 LPS 暴露雄性大鼠和 16 只 LPS 暴露雌性大鼠进一步分为盐水和 G-CSF 治疗组。

结果

在雄性大鼠中，与 LPS 暴露 G-CSF 组相比，LPS 暴露组的 TNF-α、IL-2 和 IL-17 水平显著升高。LPS 暴露 G-CSF 组雄性大鼠的神经生长因子、脑 PSD-95 和脑 GAD67 水平高于 LPS 暴露组。在雌性大鼠中，各组脑 NGF 水平相似。各组脑 GAD67 水平无差异。与 LPS 暴露组和 LPS 暴露 G-CSF 组相比，对照组雌性大鼠脑 PSD-95 水平更高。与 LPS 暴露 G-CSF 组相比，雄性大鼠 CA1 和 CA2 神经元水平较低，LPS 暴露组 CA1 和 CA3 的 GFAP 免疫染色指数（CA1）和 GFAP 免疫染色指数（CA3）较高。然而，在雌性大鼠中，各组 CA1 和 CA3 的神经元计数值无差异。